A one-pot conversion of di-substituted thiourea to O-organyl arylthiocarbamate using FeCl3

Article abstract of DOI:10.1080/17415993.2011.640328

Unsymmetrical thiourea, which on demand can generate isothiocyanate in the presence of FeCl₃, can serve as a latent isothiocyanate functionality and circumvent the difficulties associated with the direct use of reactive isothiocyanate functiona

Full text of DOI:10.1080/17415993.2011.640328

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A one-pot conversion of di-
substituted thiourea to O-organyl
arylthiocarbamate using FeCl3
Santosh K. Sahoo a , Supratim Chakraborty a & Bhisma K. Patel a
a Department of Chemistry, Indian Institute of Technology
Guwahati, Assam, India
Published online: 06 Jan 2012.
To cite this article: Santosh K. Sahoo , Supratim Chakraborty & Bhisma K. Patel (2012): A one-pot
conversion of di-substituted thiourea to O-organyl arylthiocarbamate using FeCl3 , Journal of Sulfur
Chemistry, 33:2, 143-153
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Journal of Sulfur Chemistry
Vol. 33, No. 2, April 2012, 143–153
A one-pot conversion of di-substituted thiourea to O-organyl
arylthiocarbamate using FeCl3
Santosh K. Sahoo, Supratim Chakraborty and Bhisma K. Patel*
Department of Chemistry, Indian Institute of Technology Guwahati, Assam, India
(Received 27 September 2011; final version received 7 November 2011)
Unsymmetrical thiourea, which on demand can generate isothiocyanate in the presence of FeCl3, can
serve as a latent isothiocyanate functionality and circumvent the difficulties associated with the direct use
of reactive isothiocyanate functionality. An unusual and unorthodox reactivity has been achieved during a
one-pot reaction of an unsymmetrically di-substituted thiourea with an alcohol in the presence of FeCl3
−
leading to an expeditious synthesis of O-organyl arylthiocarbamates. In this reaction, a thiono-ester (C O)
−
bond is formed at the expense of a thioamidic (C N) bond and works over a wide range of structurally
diverse thioureas and alcohols without affecting the other functional groups.
R2
R1
H
H
ROH, 30 mol% FeCl3
Acetonitrile, reflux
N
N
N
O
Ar
Ar
R
S
S
Ar = Aryl; R, R1, R2, = Alkyl
−
Keywords: green chemistry; thiourea; Fe-catalyst; arylthiocarbamate; C O bond
1. Introduction
In synthetic methodology, interconversion of one functional group to another without isolating
any intermediate is highly attractive because of higher yields of the desired product and reduced
reaction time. Recently, the focus of organic chemistry has shifted toward the development of
clean, fast, efficient, and selective processes for organic transformations and this has increased
the demand for metal-based “reaction-promoters”, especially ones that can be applied in catalytic
amount and/or are recyclable. Many heavy and rare earth-metal-based catalysts have been devised
with varied efficiencies for synthetic purposes and have some degree of general applicability but
suffer from one or more common drawbacks, including moisture sensitivity, toxicity, high cost,
harsh reaction conditions, or incompatibility with acid- or base-sensitive functional groups. In
addition, handling these catalysts often requires the use of special and expensive instrumen-
tal techniques. Consequently, new atom-efficient, cost-effective, environmentally benign, and
*Corresponding author. Email: patel@iitg.ernet.in
ISSN 1741-5993 print/ISSN 1741-6000 online
© 2012 Taylor & Francis
http://dx.doi.org/10.1080/17415993.2011.640328
http://www.tandfonline.com

144 S.K. Sahoo et al.
broad functional-group-compatible catalysts are of utmost importance from a green chemistry
perspective. Iron exactly fits into this role. It is one of the most abundant metals on earth and con-
sequently one of the most inexpensive and environmentally friendly one (1). In addition, many
iron salts and complexes are commercially available and their reactivities are well documented
in the literature (2). Iron (III) chloride and other iron (III) salts are generally strong and hard
Lewis acids. They also behave as BrØnsted acids in the presence of various alcohols. These prop-
erties make iron (III) salts extraordinary catalysts in the presence of carbonyl and thiocarbonyl
compounds. Consequently, a variety of iron (III) species are formed when iron (III) salts coor-
dinate with hard Lewis bases, viz. simple adduct with donors, for example, FeCl3(THF)3, basic
carboxylates of the type [Fe3O(O2CR)6L3]+, bent bridged species, like [(sal2en)Fe]2(μO), and
linear bridged species of the type (porph Fe)2(μ-X) (X = O, N, and C) (1, 3). Also, polymeric
oxo species such as Fe11O6(PhCO2)15(OH)6 are well documented in the literature (3c).
In the last decade, iron (III) chloride and other iron (III) salts have emerged as a very important
catalyst of choice for various synthetically useful organic transformations (4). Recently, Bolm
and co-workers presented mild and practical inter- and intramolecular cross-coupling reactions
−
−
−
that formed aryl–heteroatom bonds (e.g. C N, C S, and C O) utilizing FeCl3 (5). Kerr and
co-workers reported the use of FeCl3 for the nucleophilic displacement of azide by dimethyl
hydrazide (6).
Thiocarbamates, whichexistintwoisomericformsviz. O-Organylthiocarbamate andS-organyl
thiocarbamate (Figure 1), are a very important class of organo-sulfur compounds. The O-organyl
thiocarbamates can isomerize to S-organyl thiocarbamates via different types of thione-thiol
rearrangements. For example, the Miyazaki–Newman–Kwart rearrangement (7) is a type of rear-
rangement in which the aryl group of O-aryl thiocarbamate migrates from the oxygen to the sulfur
atom, forminganS-arylthiocarbamate.Therearrangementcanbeviewedasanintramoleculararo-
matic nucleophilic substitution favored both kinetically as well as thermodynamically. Kinetically,
the stronger nucleophilicity of sulfur compared with oxygen and thermodynamically, formation
=
=
of the more stable C O bond from the C S bond (ꢀH ∼ 13 kcal/mol) are the impetus for this
transformation (8).
Recently, there has been an increasing interest in thiocarbamates due to their newly found
ability to act as inhibitors in various biological processes (9). Alkyl-N-phenyl thiocarbamates
represent a biologically important subclass of thiocarbamates. Lu et al. described alkyl-N-phenyl
thiocarbamates as active site-binding inhibitors that are probably alkyl-chain binding-site-directed
inhibitors for enzymes such as porcine pancreatic cholesterol esterase and Pseudomonas species
lipase (10). The inhibitory effect of alkyl-N-phenylthiocarbamates (alkyl = methyl–butyl) on the
photosynthetic electron transport in plants were studied by Macho and co-workers (11) and were
found to be quite effective. One very useful drug of this thiocarbamate family is Tolnaftate
(Figure 2), which is an effective anti-fungal drug, used to treat jock itch, athlete’s foot, and
ringworm (12). Use of thiocarbamates as pesticides and insect repellent is also well known (13).
A synthetically important compound of this class is the BINOL analog (Dimethyl-thiocarbamic
acid-O-(2ꢀ-dimethylthiocarbamoyloxy-[1,1ꢀ]binapthaleryl-2-yl)ester), which is used as a chiral
ligand for various asymmetric syntheses (14).
O
S
R
R
R
R
S
N
R
N
R
O
O-organyl
thiocarbamate
S-organyl
thiocarbamate
Figure 1. Two isomeric thiocarbamates.

Journal of Sulfur Chemistry 145
S
S
Me
N
N
N
O
O
O
S
Tolnaflate
O-2-napthyl methyl(3-methylphenyl)
thiocarbamate
DTAB
Dimethyl-thiocarbamic acid-O-(2'-dimethylthio
carbamoyloxy-[1,1']binapthaleryl-2-yl)ester
Figure 2. Synthetically important thiocarbamates.
A number of methods have been reported for the preparation of O-organyl aryl thiocarbamates.
Among those, the most convenient procedures utilize the reaction between aryl isothiocyanates
and the corresponding alcohols under various conditions, viz. in the presence of a strong base (by
generating alkoxide anion) at an elevated temperature, under microwave irradiation and neutral
conditions using a large excess of alcohol (15). One major drawback of using neutral conditions is
that symmetrical 1,3-disubstituted thioureas are formed as byproducts when small chain alcohols
react with N-aryl-O-alkyl thiocarbamates. In another approach, treatment of thiocarbamic acid
chloride with alcohols under strongly alkaline conditions generate thiocarbamate adducts (16).
In contrast to thiocarbamic acid chlorides, unsymmetrical di-substituted thioureas with one side
substituted with a secondary amine are not expected to undergo a similar reaction with loss of
the secondary amine because of the poor leaving ability of its corresponding anion compared
to chloride.
In an earlier study, Konig and co-workers (17a) developed a method for the direct single-
step conversion of di-substituted thioureas to O-organyl thiocarbamates. The transformation
was done in an unconventional way using the corresponding ether of an alcohol in the pres-
ence of concentrated mineral acid at an elevated temperature. Similarly, N-arylthiocarbamates
in trichlorosilane in the presence of triethylamine is directly converted to a thiourea adduct via
an isothiocyanate intermediate (17b). The reported methods are useful but have limited substrate
scope and utilize harsh reaction conditions which can easily lead to other major side reactions.
The use of anhydrous iron (III) chloride as a reagent of choice in place of mineral acids in Friedel–
Crafts alkylation and acylation reactions are well known in the literature (18). In another instance,
Weng et al. (19) described a mild but expedient transesterification technique using Fe (III) chlo-
ride in the presence of β-diketonate ligands. Taking cues from the reported use of FeCl3 in place
of mineral acids in a number of transformations, we envisaged the development of a one-pot
strategy to synthesize thiocarbamates from di-substituted thioureas. The potential advantage of
this strategy would be to use less reactive thioureas as a dormant isothiocyanate functionality that
could be introduced early in a synthesis and carried forward through subsequent steps prior to
the liberation of isothiocyanate in a penultimate step. In this context, the thiourea acts as a stable
protected isothiocyanate functionality that can liberate isothiocyanate if desired and thus reactions
directly using reactive isothiocyanate can be minimized.
2. Results and discussion
In a typical reaction, di-substituted thiourea N-phenylpiperidine-1-carbothioamide (1a) (2 mmol)
was dissolved in ethanol (2.5 ml) to which was added FeCl3 (30 mol%), under stirring at room
temperature.After a prolonged reaction time (24 h), the product was obtained in 10% yield leaving
much of the starting material unreacted. From subsequent temperature optimization studies, it was
found that the reaction gave the best yield when performed at 80 ◦C using a shorter reaction time of

146 S.K. Sahoo et al.
6 h. To find out the role of FeCl3, the reaction was performed with different concentrations of FeCl3
(e.g. 5%, 10%, 15%, 20%, 25%, 30%, and 40%). Although the use of both 25 mol% and 30 mol%
of FeCl3 afforded identical yields (75% and 77%, respectively), the reaction with the smaller
amount of FeCl3 took longer (12 h versus 6 h) and in the absence of FeCl3 the thiocarbamate
product did not form at all. The reaction was found to be less effective using other iron salts
such as Fe(NO3)2.9H2O and Fe3O4 giving 57% and 51% yield, respectively. Control experiments
using an equivalent amount of HCl revealed the role of acid in the reaction but the yield was poor
(22%), thus confirming that Fe has a role other than just liberating HCl in the medium. According
to previous studies, ligands improve the efficiency of iron-catalyzed carbon–heteroatom bond
forming reactions (5). We were interested to find out if the same is true for our reactions as well.
A study combining 30 mol% FeCl3 and two different ligands methylacetoacetate (30 mol%) and
1,10-phenanthroline (30 mol%) were conducted. To our surprise, the ligands failed to show the
expected efficacy and both gave messy reactions mixtures giving undesirable side products and
only 42% and 46% of the desired product (1a).
The use of neat alcohol, as described above, when more expensive alcohols are needed, is not
economically feasible. Consequently, we have also explored the use of co-solvents. Among the
five different polar aprotic solvents tested, acetonitrile was found to be the most effective giving
a 77% yield of (1a). Very low conversions were obtained using THF and acetone (14% and 31%
respectively), while in polar solvents such as DMF and DMSO moderate yields of 45% and 41%
were obtained, respectively.
With the optimum protocol in hand, different types of alcohols as the nucleophiles and dif-
ferent secondary amines attached to the thiourea were explored, while keeping the aryl side
of the thiourea constant. As shown in Table 1, a variety of aliphatic primary and secondary
alcohols react efficiently giving moderate to good yields of the product. The bulky alcohol,
cyclohexanol, afforded lower yields compared with linear primary alcohols. The structure O-
cyclohexyl N-phenylcarbamothioate (1d) has been confirmed by X-ray crystallography as shown
in Figure 3. Piperidine-derived thiourea (1) gave better yields compared with morpholine (2)
and N, Nꢀ-diethylamine (3) derived thioureas. Thus, the reactivity order follows the trend piperi-
dine ꢁ N, Nꢀ-diethylamine > morpholine. The lower reactivity of morpholine may be due to its
low donor and coordination ability, especially in the presence of alcohols.
Various unsymmetrical 1,3-di-substituted thioureas with diverse functionality on the aryl ring
were subjected to the optimized reaction conditions in order to understand the effect of various
substituents. For all of these reactions, piperidine-derived thioureas (4–9) were chosen as the
outgoing secondary amine and heptanol as the incoming alcohol. As summarized in Table 2, all
−
−
−
the substrates possessing weakly electron-donating group Me (4), OMe (5), n-Bu (6) react
efficiently giving the corresponding products (4c), (5c), and (6c), respectively. Similarly, sub-
−
−
strates bearing weakly deactivating substituents Cl (7), F (8), and 4-bromo-2-fluoro (9), all
gave the expected products in moderate yield under the optimized reaction conditions (Table 2).
It was observed that electron-donating substituents in the aryl ring gave somewhat better yield
(ranging from 72% to 92%) compared with substrates possessing electron-withdrawing sub-
stituents (ranging from 61% to 73%). The aryl ring containing two electron-withdrawing groups
(4-bromo-2-fluoro) (9) gave the lowest yield.
Recently, we have synthesized an interesting class of thiourea having an aryl group on one side
andacyclicguanidinemoiety(assecondaryamine)ontheotherside, calledimidazolidenecarboth-
ioamides (20). We were interested to see whether a cyclic guanidine containing secondary amine
can be displaced with primary alcohols. It is heartening to note that thioureas (10)–(12) containing
a cyclic guanidine underwent smooth transformations to give the corresponding thiocarbamates
(1c), (4c), and (8c), respectively, demonstrating the power of the methodology (Table 3).
We suggest the mechanism shown in Scheme 1 for this new reaction. This suggestion is based
upon the previous report that iron (III) species tend to hydrolyze in the presence of water or

Journal of Sulfur Chemistry 147
Table 1. Synthesis of thiocarbamates from disubstituted thioureas.a
R1
R2
H
H
30 mol% FeCl3
N
N
N
O
ROH
Ph
Ph
+
R
Acetonitrile, reflux
S
S
Substrate
Alcohol
Productb
Time (h)
Yield (%)c
H
N
O
Ph
Ph
Ethanol
6
77
82
(1a)
S
S
H
N
O
( )3
(1b)
Butanol
6.5
H
N
N
Ph
H
N
O
S
(1)
( )6
(1c)
Ph
Heptanol
6
7
95
65
S
S
H
N
O
Cyclohexanol Ph
(1d)
H
N
O
Ethanol
Butanol
Ph
Ph
8.5
8
51
59
(1a)
S
S
H
N
O
( )3
(1b)
H
N
N
Ph
O
H
N
S
(2)
O
( )6
(1c)
Heptanol
Ph
Ph
9
9
64
49
S
S
H
N
O
Cyclohexanol
(1d)
H
N
O
Ethanol
Butanol
Ph
Ph
7
61
71
(1a)
S
S
H
N
O
H
( )3
N
N
6.5
Ph
(1b)
(3)
S
H
N
O
( )6
(1c)
Heptanol
Ph
Ph
8
81
55
S
S
H
N
O
Cyclohexanol
7.5
(1d)
Notes: aReactions were performed in presence of excess (5 equiv.) alcohol and were
monitored by TLC; bConfirmed by 1H and 13C NMR; cYield after column chromatography.
alcohols into oxophilic doubly μ-hydroxo or μ-alkoxy species (21) and on other mechanistic
studies of iron alkoxide-catalyzed reactions (19) and on the observation of the formation of
trace amount of aryl isothiocyanate in the reaction mixture (confirmed by checking GC and IR).
According to this mechanistic speculation, the main species that serves as the active reaction
promoter is not the monomeric iron (III) chloride but the dimeric iron (III) μ-alkoxy species.

148 S.K. Sahoo et al.
Figure 3. ORTEP view of (11d).
Table 2. Synthesis of thiocarbamates from disubstituted thioureas.a
H
H
Heptanol, 30 mol% FeCl3
Acetonitrile, reflux
N
O
N
N
( )6
Ar
Ar
S
S
Substrate
Product
Time (h)
8
Yield (%)c
72
H
H
N
N
N
O
( )6
(4)
(4c)
S
S
Me
O
Me
O
H
H
N
N
N
O
( )6
6
6.5
8
84
92
73
70
61
(5)
(5c)
S
S
H
N
H
N
N
O
( )6
(6)
(6c)
S
S
( )3
( )3
H
H
N
N
N
O
( )6
(7)
(7c)
S
S
Cl
Cl
H
H
N
N
N
O
( )6
(8c)
8
(8)
S
S
F
F
H
H
N
N
N
O
( )6
(9c)
10
(9)
S
S
Br
F
Br
F
Notes: aReactions were performed in the presence of excess (5 equiv.) alcohol and were monitored by TLC;
bConfirmed by 1H and 13C NMR; cYield after column chromatography.
Initial dissociation of the monomeric iron (III) chloride driven by nucleophilic substitution of
the alcohol leads to the formation of the μ-alkoxy dimer (I) that serves as the active reaction
promoter and activates the di-substituted thiourea to generate the cationic adduct (II). Proton
transfer, either intra or intermolecular, then leads to the formation of species (III). In the next
step, intramolecular nucleophilic attack of the coordinated alcohol to the sterically congested iron

Journal of Sulfur Chemistry 149
Table 3. Synthesis of thiocarbamates from imidazolidenecarbothioamides.a
Ph
N
H
H
Heptanol, 30 mol% FeCl3
Acetonitrile, reflux
N
NH
N
O
N
( )6
Ar
Ar
S
S
Substrate
Product
Time (h)
10
Yield (%)c
Ph
N
H
H
N
N
NH
N
O
72
( )6
(1c)
S (10)
S
Ph (p-Me)
N
H
N
H
N
N
NH
O
( )6
10.5
12
69
64
(11)
S
S
Me
Me
(4c)
Ph (p-F)
N
H
H
N
N
NH
N
O
( )6
(8c)
S
S
(12)
F
F
Notes: aReactions were performed in the presence of excess (5 equiv.) alcohol and were monitored by TLC.
bConfirmed by 1H and 13C NMR.
cYield after column chromatography.
FeL3
L = Cl
ROH
L-H
H
R
O
N
N
,
N C S
Ar
Ar
H
(L)2Fe
Fe(L)2
S
N
O
R
I
R
O
R
ROH
HL
O
(L)2Fe
N
Fe(L)2
(L)2Fe
S
Fe(L)2
IV
II
O+
R
O
+
Ar
H
S
R
N
N
Ar
HN
III
H
N
O
R
O
Ar
R
S
(L)2Fe
S
Fe(L)2
O+
H
R
N
N
Ar
Scheme 1. Proposed catalytic cycle for the FeCl3 promoted synthesis of thiocarbamate.
center and concomitant elimination of secondary amine from the coordinated thiourea lead to the
formation of arylisothiocyanate. This then reacts with the free alcohol to afford the thiocarbamate
adduct.
On the basis of this proposed mechanism, we can interpret our previous observation that the
reaction efficiency drastically changes with the identity of the secondary amine substituents in

150 S.K. Sahoo et al.
the order piperidine ꢁ N, Nꢀ-diethylamine > morpholine. In the case of N, Nꢀ-diethylamine, the
free rotation of two ethyl groups destabilizes the cationic species (IV) (as in Scheme 1) due to
steric congestion. This effect of steric hindrance is less prominent in the piperidine ring system
that can be considered as a diethyl substituent with the two ethyl groups tied together to prevent
rotation. Among all the three secondary amines, morpholine showed the least efficiency in the
reaction. This can be explained by considering the high oxophilicity of iron (III), which promotes
coordination with the oxygen atom of morpholine, thus preventing the formation of an effective
reaction promoter iron (III) μ-alkoxy species (I).
3. Conclusion
In conclusion thiourea serves as latent isothiocyanate functionality which can be converted to
O-organyl arylthiocarbamates under mildly acidic conditions; thus, the problem associated with
the direct use of reactive isothiocyanate functionality can be avoided. The iron (III) catalyst
system has several exciting features, including a high tolerance for diverse functional groups, cost-
effectiveness, high yields and environmental-friendliness compared with the other conventional
approaches.
4. Experimental
All the reagents were of commercial grade and purified according to established procedures.
Organic extracts were dried over anhydrous sodium sulfate. Solvents were removed in a rotary
evaporator under reduced pressure. Reactions were monitored by TLC on silica gel 60 F254
(0.25 mm). Column chromatography was performed using silica gel (60–120 meshes). NMR spec-
tra were recorded in CDCl3 with tetramethylsilane as the internal standard for 1H NMR (400 MHz)
and 13C NMR (100 MHz); the chemical shifts are expressed as δ values (ppm). HRMS spectra
were recorded using WATERS MS system, Q-Tof premier and data analyzed using Mass Lynx
4.1. Melting points were recorded in a Buchi B-545 melting point apparatus and are uncorrected.
IR spectra were recorded in KBr or neat on a Nicolet Impact 410 spectrophotometer.
4.1. General procedure for the preparation of phenyl-thiocarbamic acid O-heptyl ester from
piperidine-1-carbothioic acid phenylamide
To a solution of piperidine-1-carbothioic acid phenylamide (1) (0.44 g, 2 mmol) in acetonitrile,
heptanol (1.16 g, 10 mmol) and anhydrous FeCl3 (0.10 g, 0.6 mmol) was added and the reaction
mixture was stirred constantly under open atmosphere. After 6 h, the mixture was mixed with
water (1 ml) and the product extracted with ethyl acetate (2 × 10 ml). The ethyl acetate layer
was washed with saturated sodium bicarbonate solution (2 × 2 ml). The organic layer was dried
over anhydrous sodium sulphate (Na2SO4), filtered, and evaporated under reduced pressure. The
product so obtained was sufficiently pure but for analytical data it was purified through a short
column of silica gel using hexane/ethyl acetate (9 : 1) as the eluent to yield the pure product
1
phenyl-thiocarbamic acid O-heptyl ester (1c) (0.477 g, 95%). White solid; m.p. 39–40 ◦C; H
NMR (400 MHz, CDCl3): δ 0.88 (t, 3H, J = 6.8 Hz), 1.28–139 (m, 7H), 1.77 (t, 3H, J = 6.8 Hz),
4.56 (s, 2H), 7.16–7.33 (m, 5H), 8.72 (brs, 1H); 13C NMR (100 MHz, CDCl3): δ 14.2, 22.6,
26.0, 28.5, 28.9, 31.7, 73.1, 121.6, 125.4, 129.1, 137.2, 188.8; IR (KBr): 3224 (m), 3120 (m),
3054 (m), 2956 (m), 2922(m), 2851(m), 1598 (s), 1548 (s), 1492 (m), 1413 (m), 1348 (m),
1192 (s), 1036 (s), 747 (s) cm−1; HRMS (ESI) calcd for C14H21NOS (M + H+) 252.1482; found
252.1478.

Journal of Sulfur Chemistry 151
4.1.1. O-Ethyl N-phenylcarbamothioate (1a)
White solid; m.p. 78–80 ◦C; 1H NMR (400 MHz, CDCl3): δ 1.40 (t, 3H, J = 6.4 Hz), 4.64 (s, 2H)
7.16 (s, 1H), 7.32 (d, 4H., J = 6.8 Hz), 9.21 (brs, 1H); 13C NMR (100 MHz, CDCl3): δ 4.2, 68.8,
121.6, 125.3, 129.0, 137.2, 188.5; IR (KBr): 3223 (s), 3106 (m), 3042 (m), 2989 (m), 2931 (m),
2864 (m), 2731 (m), 1594 (s), 1539 (s), 1462 (m), 1403 (m), 1372 (m), 1320 (m), 1291 (m), 1214
(m), 1203 (m), 1100 (m), 1041 (s), 814 (s), 742 (m) cm−1; HRMS (ESI) calcd for C9H11NOS
(M + H+) 182.0667; found 180.0670.
4.1.2. O-Butyl N-phenylcarbamothioate (1b)
Oily; 1H NMR (400 MHz, CDCl3): δ 0.87–0.97 (m, 3H), 1.40–1.44 (m, 2H), 1.73–1.78 (m, 2H),
4.58 (s, 2H), 7.21 (d, 2H, J = 7.2 Hz), 7.28 (d, 2H, J = 7.2 Hz), 7.34 (t, 1H, J = 7.6 Hz; 13C
NMR (100 MHz, CDCl3): δ 13.8, 19.2, 30.5, 72.7, 125.7, 127.3, 129.0, 129.5, 188.6; IR (KBr):
3231 (s), 3036 (m), 2958 (s), 2930 (s), 2872 (m), 1596 (s), 1538 (s), 1445 (m), 1404 (m), 1335
(m), 1188 (m), 1028 (m), 750 (m), 690 (m) cm−1; HRMS (ESI) calcd for C11H12N2S (209.09):
(M + H+) 210.0972; found 210.0978.
4.1.3. O-Cyclohexyl N-phenylcarbamothioate (1d)
Whitesolid;m.p. 76–78 ◦C;1HNMR(400 MHz, CDCl3):δ 1.25–1.79(m, 8H), 2.00–2.03(M, 2H),
5.45 (s, 1H), 7.16 (d, 1H, J = 6.0 Hz), 7.26–7.35 (m, 4H), 8.83 (brs, 1H); 13C NMR (100 MHz,
CDCl3): δ 23.7, 24.8, 25.3, 31.3, 31.7, 81.7, 121.6, 125.2, 129.0, 137.3, 187.7; IR (KBr): 3228
(s), 3121 (m), 3036 (m), 2935 (s), 2858 (s), 1712 (s), 1597 (s), 1538 (s), 1446 (m), 1391 (m), 1359
(m), 1193 (m), 1145 (m), 1044 (m), 1019 (m), 986 (m), 749 (m), 690 (m) cm−1. Anal. Calcd for
C13H17NOS (235.10): C 66.34, H 7.28, N 5.95, S 13.62; found C 66.44, H 7.35, N 5.91, S 13.53.
4.1.4. O-Heptyl N-p-tolylcarbamothioate (4c)
Oily; 1H NMR (400 MHz, CDCl3): δ 0.87 (t, 3H, J = 6.8 Hz), 1.27–1.34 (m, 4H), 1.71–1.76 (m,
2H), 2.30–1.32 (m, 6H), 4.54 (s, 2H), 7.06–7.12 (m, 4H), 8.60 (brs, 1H); 13C NMR (100 MHz,
CDCl3): δ 14.2, 21.3, 22.6, 25.9, 28.6, 31.8, 73.1, 125.6, 129.6, 130.2, 137.6, 188.7; IR (KBr):
3327 (m), 3026 (m), 2928 (s), 2856 (s), 1709 (s), 1583 (s), 1526 (s), 1453 (m), 1405 (m), 1365
(m), 1226 (m), 1208 (m), 1123 (m), 1071 (m), 816 (s) cm−1; HRMS (ESI) calcd for C15H23NOS
(M + H+) 266.1615; found 266.1618.
4.1.5. O-Heptyl N-4-methoxyphenylcarbamothioate (5c)
Oily; 1H NMR (400 MHz, CDCl3): δ 0.85 (t, 3H, J = 6.8 Hz), 1.24 (m, 8H), 1.68–1.74 (m, 2H),
3.76 (s, 3H), 4.51 (s, 2H) 6.82 (d, 2H, J = 8.0 Hz), 8.86 (brs, 1H) 13C NMR (100 MHz, CDCl3):
δ 14.1, 22.6, 25.9, 28.5, 28.9, 31.7, 55.5, 72.9, 114.2, 123.7, 126.1, 130.3, 157.3, 188.6; IR (KBr):
3231 (m), 2954 (s), 2929 (s), 2856 (m), 1596 (m), 1514 (s), 1463 (m), 1404 (m), 1366 (m), 1298
(m), 1249 (s), 1171 (s), 1037 (s), 828 (s), 735 (m) cm−1; HRMS (ESI) calcd for C15H23NO2S
(M + H+) 282.1615; found 266.1614.
4.1.6. O-Heptyl N-4-butylphenylcarbamothioate (6c)
Oily; 1H NMR (400 MHz, CDCl3): δ 0.86–0.93 (m, 8H), 1.19–1.36 (m, 10H), 1.52–1.60(m, 4H),
1.73–1.75 (m, 2H), 2.56 (t, 3H, J = 7.6 Hz), 4.55 (s, 2H), 7.02–7.25 (m, 4H), 9.21 (brs, 1H);

152 S.K. Sahoo et al.
13C NMR (100 MHz, CDCl3): δ 13.9, 14.0, 22.3, 25.9, 28.5, 28.9, 31.7, 33.5, 35.0, 49.4, 72.8,
121.6, 128.8, 134.9, 140.0, 188.5; IR (KBr): 3395 (m), 3235 (m), 3029 (m), 2955 (m), 2928 (s),
2857 (s), 1714 (m), 1592 (s), 1536 (s), 1520 (s), 1465 (m), 1403 (m), 1360 (m), 1341 (m), 1176
(s), 1042 (m), 831 (m), 725 (m) cm−1; HRMS (ESI) calcd for C18H29NOS (M + H+) 308.2106;
found 308.2109.
4.1.7. O-Heptyl N-2-chlorophenylcarbamothioate (7c)
Oily; 1H NMR (400 MHz, CDCl3): δ 0.86 (t, 3H, J = 6.0 Hz), 1.26–1.32 (m, 8H), 1.73 (t, 2H,
J = 7.2 Hz), 4.50 (t, 2H, J = 6.8 Hz), 7.06 (t, 1H, J = 7.6 Hz), 7.34 (d, 2H, J = 8.0 Hz), 8.46
(brs, 1H); 13C NMR (100 MHz, CDCl3): δ 14.0, 22.4, 25.7, 28.3, 28.7, 31.6, 72.2, 124.3, 125.4,
126.1, 127.1, 129.3, 134.0, 188.6; IR (KBr): 3397 (s), 2950 (s), 2928 (s), 2856 (s), 1592 (m), 1519
(s), 1442 (m), 1397 (m), 1360 (m), 1333 (m), 1179 (m), 1033 (m), 750 (m) cm−1; HRMS (ESI)
calcd for C14H20NOSCl (M + H+) 286.1074; found 286.1079.
4.1.8. O-Heptyl N-4-fluorophenylcarbamothioate (8c)
Oily; 1H NMR (400 MHz, CDCl3): δ 0.82–0.92 (m, 2H), 1.27 (s, 9H) 1.62–1.74 (m, 2H), 4.14 (s,
2H) 6.90–7.02 (m, 2H), 7.23–7.32 (m, 2H),9.18 (brs, 1H) ; 13C NMR (100 MHz, CDCl3): δ 14.1,
22.6, 25.9, 28.5, 29.0, 73.1, 115.7 (d, 2JCF = 88.4 Hz), 115.9 (d, 2JCF = 88.4 Hz), 120.6, 123.9,
134.1, 160.2 (d, 1JCF = 964 Hz), 188.9; IR (KBr): 3434 (s), 2961 (m), 2928 (s), 2857 (m), 1704
(m), 1613 (s), 1531 (m), 1410 (m), 1300 (m), 1211 (s), 1068 (m), 833 (s), 768 (m), 725 (m), 511
(m) cm−1; HRMS (ESI) calcd for C14H20NOSF (M + H+) 270.1330; found 270.1335.
4.1.9. O-Heptyl N-4-bromo-2-fluorophenylcarbamothioate (9c)
Oily; 1H NMR (400 MHz, CDCl3): δ 0.83–0.90 (m, 3H), 1.25–1.35(m, 8H), 1.65–1.78 (m, 2H),
4.11–4.18 (m, 2H), 7.20–7.29 (m, 3H), 7.99 (brs, 1H); 13C NMR (100 MHz, CDCl3): δ 14.1,
22.6, 25.9, 28.5, 28.9, 31.7, 72.7, 118.5 (2JCF = 88.4 Hz), 119.2 (d, JCF = 91.6 Hz), 121.3,
2
125.0, 127.6, 153.3, 188.7; IR (KBr): 3426 (s), 2955 (s), 2928 (s), 2856 (s), 1737 (m), 1614 (m),
1591 (m), 1519 (s), 1396 (m), 1338 (m), 1231 (s), 1183 (m), 1069 (m), 881 (m), 855 (m), 811
(m) cm−1; HRMS (ESI) calcd for C14H19NOSBrF (M + H+) 348.0505; found 348.0505.
Acknowledgements
B.K.P. acknowledges the support of this research from DST New Delhi (SR/S1/OC-79/2009) and CSIR
01(2270)/08/EMR-II. S.K.S. thanks CSIR for fellowships. Thanks are due to Central Instruments Facility (CIF), IIT
Guwahati, for NMR and mass spectra and DST-FIST for XRD facility.
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(22) CCDC numbers for compound 1d: CCDC 828383. These data can be obtained free of charge from the Cambridge
Crystallographic Data Centre via www.ccdc.cam.ac.uk/datarequest/cif. Crystallographic description of 1d: Crys-
tal dimension (mm): 0.43 × 0.35 × 0.26. C13H16N1O1S1, Mr = 234.34. Monoclinic, space group P2(1)/n; a =
10.1039(19)Å, b = 18.054(4)Å, c = 14.444(3)Å; α = 90.00◦, β = 99.687(10), γ = 90.00◦, V = 2597.2(9)Å3;
Z = 8; ρcal = 2.26 mg/m3; μmm−1) = 1.199; F (000) = 1000; reflection collected/unique = 6538/3452; refine-
ment method = full-matrix least-squares on F2; final R indices [I > 2σl] R1 = 0.1325, wR2 = 0.2032, R indices (all
data) R1 = 0.0724, wR2 = 0.1741; goodness of fit = 0.997.