An "on-water" exploration of CuO nanoparticle catalysed synthesis of 2-aminobenzothiazoles

Article abstract of DOI:10.1039/c2gc35575b

An "on-water" one-pot process has been engineered for the preparation of 2-aminobenzothiazole from ortho-halo (-F, -Cl, -Br and -I) substituted unsymmetrical thioureas. For ortho -I and -Br substrates the reactions afford 2-aminobenzothiazoles under metal free condition promoted by base. However, the relatively inert ortho -Cl and -F substrates undergo intramolecular arylthiolation only in the presence of CuO nanoparticles yielding 2-aminobenzothiazoles. This methodology provides easy access to aminobenzothiazoles utilising even the ortho -Cl and -F substrates. The catalyst is recyclable several times without loss of substantial activity. Other remarkable features include the wide range of functional group tolerance, absence of chromatographic purification (for ortho -I and -Br substrates) and providing moderate to excellent yield of the products under mild conditions, thus rendering the methodology as a highly eco-friendly alternative to the existing methods.

Full text of DOI:10.1039/c2gc35575b

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PAPER
An “on-water” exploration of CuO nanoparticle catalysed synthesis of
2-aminobenzothiazoles†‡
Saroj Kumar Rout, Srimanta Guin, Jayashree Nath and Bhisma K. Patel*
Received 17th April 2012, Accepted 8th June 2012
DOI: 10.1039/c2gc35575b
An “on-water” one-pot process has been engineered for the preparation of 2-aminobenzothiazole from
ortho-halo (–F, –Cl, –Br and –I) substituted unsymmetrical thioureas. For ortho –I and –Br substrates the
reactions afford 2-aminobenzothiazoles under metal free condition promoted by base. However, the
relatively inert ortho –Cl and –F substrates undergo intramolecular arylthiolation only in the presence of
CuO nanoparticles yielding 2-aminobenzothiazoles. This methodology provides easy access to
aminobenzothiazoles utilising even the ortho –Cl and –F substrates. The catalyst is recyclable several
times without loss of substantial activity. Other remarkable features include the wide range of functional
group tolerance, absence of chromatographic purification (for ortho –I and –Br substrates) and providing
moderate to excellent yield of the products under mild conditions, thus rendering the methodology as a
highly eco-friendly alternative to the existing methods.
Various pharmacophores bearing this heterocyclic unit have
revealed a broad spectrum of biological activities that encompass
Introduction
In recent years, many efforts have been devoted towards sustain-
anti-inflammatory, anti-microbial, anti-tumour, neuroprotective
and anti-convulsant activities.4 Instances of the recent develop-
able reaction media, and notably the use of water as solvent has
grabbed considerable interest among the synthetic community.1
ments of the pharmacophores possessing the 2-aminobenzothia-
Indeed, water as a solvent offers many advantages because it is
cheap, readily available, non-toxic and non-flammable, thus being
very attractive from both an economical and environmental point
of view. In addition, water is also recognized as an effective reac-
tion medium with unique properties for many organic reactions
that cannot be attained in conventional organic solvents.1d,e,2 It is
believed, particularly for on-water reactions, that the hydrophobic
effect of water generates an internal pressure which brings the
reactants into close proximity and promotes the association of
reactants in solvent cavities during reaction processes and thus
accelerates reactions.1c,h,3 As a result, tremendous efforts have
been implemented in the development of catalytic processes by
employing water as a medium to accomplish greener syntheses. A
query that exists is how far the on-water catalytic processes could
be engineered to benefit the synthesis of biologically important
pharmacophores. To speak of bioactive molecules, substituted
benzothiazoles display a diverse array of such compounds. In this
regard, 2-aminobenzothiazoles have attracted particular attention
as they comprise the privileged motifs prevalent in various
pharmaceutical and agrochemical compounds.
zole as the core unit include a potent inhibitor of all trans-
retinoic acid metabolism (1),4d the antibacterial compound (2),5
the PPAR agonist (3),6 the H3-receptor ligand (4),7 the nicotinic-
acetylcholine-receptor ligand (5),8 and activity for enhancing the
atRA-induced expression of CYP26B1 (6)4e as shown in Fig. 1.
The potential of the 2-aminobenzothiazoles has led to them
being encountered through the development of various synthetic
protocols. The classical methodologies employed for their syn-
thesis involve (i) transition metal-catalyzed intramolecular
Department of Chemistry, Indian Institute of Technology Guwahati, 781
039 Assam, India. E-mail: patel@iitg.ernet.in; Fax: +91-3612690762
†Electronic supplementary information (ESI) available: 1H and 13C
NMR spectra and HRMS spectra. CCDC 876212 and 829313. For ESI
and crystallographic data in CIF or other electronic format see DOI:
10.1039/c2gc35575b
‡This manuscript is dedicated to Prof. Rajani Kanta Behera on the
occasion of his 60th birthday.
Fig. 1 Structures of bioactive 2-N-substituted benzothiazoles.
Green Chem., 2012, 14, 2491–2498 | 2491
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copper have been successfully exploited for various C–N, C–O,
C–S cross-coupling reactions.14,18 It is worth mentioning here
that CuO nanoparticles as catalysts have been able to provide the
platform to realise the carbon heteroatom bond formation
through a dehalogenative path of the relatively inert C–F and
C–Cl bond under mild conditions.18d,e The tendency of Cu as
compared to Pd towards dehalogenative path over a C–H acti-
vation has been very recently demonstrated by us.19
Hence, judging the rationale behind the development of a
versatile and sustainable methodology and our interest on the
exploration of expeditious synthesis of heterocyclic frame-
works,19,20 we have envisioned a practical, greener route to
2-aminobenzothiazoles via a water mediated tandem reaction of
2-haloarylisothiocyanates with various amines. Herein, we report
our observations in this regard.
Scheme 1 Available literature methods for the preparation of 2-amino
benzothiazoles.
cyclisation of 2-halobenzothioureas (path a, Scheme 1),9
(ii) coupling of arylamines with preformed 2-halobenzothiazoles
(path b, Scheme 1)10 or 2-aminobenzothiazoles with aryl
halides, (path c, Scheme 1)11 and (iii) oxidative cyclisation of
thiobenzanilides including Jacobson’s and Hugerschoff’s
methods (path d, Scheme 1)12 or the intermediates generated by
2-aminothiophenols with isothiocyanates (path e, Scheme 1).13
Although these methods are generally efficient and high yield-
ing, a careful scrutiny would entail that most of the strategies
suffer some setback owing to their limited utility and applica-
bility in large and industrial scale applications. This is because
they usually employ highly toxic and corrosive reagents, expens-
ive catalyst systems, drastic reaction conditions or generate
environmentally hazardous wastes. To circumvent these dis-
advantages various modified protocols were being explored that
involve the use of recyclable catalysts under ligand-free condi-
tions13a,14 the C–H activation strategy15 or the metal-free base-
mediated conditions16 to promote intramolecular C–S bond
forming reactions. Despite there being a subtle improvement of
the reaction conditions through these strategies, somewhere
down the line they still lack the versatility. The most concerning
outcome is the detrimental effect of environmentally non-compa-
tible solvents. Secondly, the catalyst systems are usually non-
recoverable, thereby reducing the turn over number (TON) or
turn over frequency (TOF) which are important from an indus-
trial point of view. Also worth mentioning is that most of the
literature methods focused on the cross-coupling reactions of
more labile o-iodo or o-bromo substrates. Hence they are devoid
of substrate generality as the inert C–Cl and C–F bonds are over-
looked most of the time. In this regard the C–H activation strat-
egy seems advantageous due to operational simplicity and
avoiding the arduous substrate pre-activation steps, however,
they make use of highly oxidised conditions which are undesir-
able in pharmaceuticals. Therefore it is of utmost importance to
develop economically and environmentally more viable pro-
cedures for the synthesis of 2-aminobenzothiazoles.
Results and discussion
To examine the feasibility of CuO catalysed reaction on water,
an initial experiment was performed with o-iodophenyl isothio-
cyanate (1) and morpholine (a) as the model substrate. Upon
treatment of o-iodophenylisothiocyanate 1 (1 equiv.) with
morpholine (a) (1 equiv.) under neat condition provided the
intermediate thiourea which was then subjected to cross-coupling
reaction following subsequent addition of K2CO3 (1 equiv.) and
catalyst CuO nanoparticles (2.5 mol%) in aqueous medium.
No reaction was observed at room temperature but by performing
the reaction at 80 °C (Table 1, entry 2) encouragingly the reac-
tion afforded the corresponding product 2-aminobenzothiazole
1a via intramolecular cyclisation in 80% yields within 1.5 h.
With further increase in temperature to 100 °C the yield
increased to 95% within a shorter span of 30 min (Table 1, entry
3). A decrease in the catalyst amount to 2 mol% provided a con-
sistent result without alteration of yield (Table 1, entry 4). With
the initial results in hand, a series of experiments were performed
by varying solvents, temperature, catalyst quantity and bases to
arrive at the best optimal reaction conditions and establish the
superiority of water as solvent compared to commonly employed
organic solvents. The results are summarised in Table 1. Entries
4 and 9 (Table 1) show that both water and DMSO were equally
effective in giving good yields in short reaction time while both
K2CO3 (Table 1, entry 4) and Cs2CO3 (Table 1, entry 6) could
be used as the base of choice when 2 mol% of the catalyst was
used. It is noteworthy that when a blank reaction (without CuO)
was performed (Table 1, entry 13) a low conversion of the
product (1a) was obtained. On increasing the base quantity to
3 equivalents the yield enhanced to 94% within 3 h (Table 1,
entry 15). Hence considering the Green Chemistry criteria, we
opted to choose water as solvent and K2CO3 as the base under
metal-free conditions (Table 1, entry 15) for subsequent studies
of the o-iodo substrates. It may be mentioned here that a metal
free synthesis of 2-substituted benzothiazoles has been achieved
via base promoted cyclisation in organic solvent dioxane having
2-bromo and 2-iodo substrates at 130 °C in a sealed tube.16c
In this “on water” reaction the starting materials thiourea remains
insoluble in water and so is the product which can be filtered
out. Alternatively it can be extracted out from the reaction
mixture with ethyl acetate leaving behind the aqueous
On the other hand, nano-crystalline metal oxides bearing high
surface area and reactive morphologies find excellent appli-
cations as catalysts for various organic transformations.17 Fur-
thermore, the nano-material catalysed reactions provide the
advantages of high atom efficiency, simplified isolation of
product, and easy recovery and recyclability of the catalysts.
These features of the nano-materials, in particular the salts of
2492 | Green Chem., 2012, 14, 2491–2498
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Table 1 Optimisation of reaction conditionsa
After having successfully established the reaction with the
o-iodo substrates, next we executed the reaction onto the
o-bromo substrates. It was delightful to observe that the opti-
mised condition could be equally applicable to the 2-bromo
substituted thioureas however being slightly sluggish compara-
tive to the o-iodo substrates. The reaction of 2-bromophenyliso-
thiocyanate (4) with either aliphatic secondary amines (a, h–i) or
primary amines (e, j–k) afforded corresponding thioureas in situ
which underwent the intramolecular cyclisation providing the
desired products in good to excellent yields. This reveals the ver-
satility of this protocol.
Catalyst
Entry (mol%)
Base
Solvent (equiv.)
Yieldb
Time (h) (%)
Temp
1.
2.
3.
4.
5.
6.
7.
8.
CuO (2.5) H2O
CuO (2.5) H2O
CuO (2.5) H2O
K2CO3 (1) 30 °C
K2CO3 (1) 80 °C
K2CO3 (1) 100 °C 0.5
K2CO3 (1) 100 °C 0.5
K2CO3 (1) 100 °C
Cs2CO3 (1) 100 °C 0.5
5
00
80
95
95
77
96
65
40
92
70
55
63
20
60
94
1.5
In order to reveal further scope of this methodology we turned
our attention to the ortho-chloro substrates. An attempt to effect
the intramolecular arylthiolation with the in situ generated
o-chlorothiourea obtained by reacting 2-chlorophenylisothiocya-
nate (7) and morpholine (a) (Table 3, entry 1) under the above
standardised condition provided inferior results as no conversion
was observed at all even after 24 h. This observation indicates
the degree of inertness of the C–Cl bond toward the intramole-
cular cyclisation (C–Cl bond energy 95 kcal mol−1) under metal
free condition. Hence, the use of the catalytic CuO nanoparticle
was thought to facilitate the transformation. To examine the
effect of catalyst the in situ generated o-chloro thiourea obtained
by reacting 2-chlorophenylisothiocyanate (7) and morpholine (a)
with 2 mol% of the catalyst provided the desired product (1a) in
decent yield of 68% (Table 3, entry 2) along with the formation
of undesired decomposition products. When the catalyst amount
was increased to 2.5 mol% there was marginal improvement of
yield up to 72% (Table 3, entry 3). Surprisingly, increase in cata-
lyst loading (beyond 5 mol%) had rather adverse effect on the
product yield. The yield dropped resulting in the formation of
undesirable side products (Table 3, entry 6 and entry 7). It is
worth mentioning that the increase in catalyst quantity increased
the rate of conversion, however, it was disadvantageous with
respect to the formation of side products. Hence to suppress the
formation of the multitude of undesired products, for subsequent
investigation 2.5 mol% of the catalyst was used along with
1.5 equivalent of base (Table 3, entry 5). 2-Chloroisothiocyanate
(7) was treated with different aliphatic secondary (a, l, m,
Table 4) and primary (e, n–p, Table 4) amines to generate corres-
ponding thioureas in situ. The reaction of resulting in situ
thioureas in the presence of CuO nanoparticle catalyst proceeded
well to give their respective benzothiazoles in moderate to good
yields as shown in Table 4. Also, the in situ generated thioureas
derived from electron-rich (8) and electron-deficient (9) isothio-
cyanates and aliphatic secondary amine (a) underwent this trans-
formation giving corresponding benzothiazoles (8a) and (9a)
respectively, in modest yield.
CuO (2)
CuO (1)
CuO (2)
CuO (2)
CuO (2)
CuO (2)
CuO (2)
CuO (2)
CuO (2)
Nil
H2O
H2O
H2O
H2O
H2O
2
NaOH (1)
Et3N (1)
100 °C
100 °C
2
2
9.
DMSO K2CO3 (1) 100 °C 0.5
DMF
Toluene K2CO3 (1) 100 °C
Dioxane K2CO3 (1) 100 °C
H2O
H2O
H2O
10.
11.
12.
13.
14.
15.
K2CO3 (1) 100 °C
2
2
2
7
5
3
K2CO3 (1) 100 °C
K2CO3 (2) 100 °C
K2CO3 (3) 100 °C
Nil
Nil
a Reactions were monitored by TLC. b Isolated yield.
suspension CuO catalyst for further round of reaction, thus an
excellent demonstration of “on water” reaction.
With the optimal “on water” reaction conditions established,
we sought to investigate the scope and generality of this methodo-
logy. The results shown in Table 2 attest that this methodology is
compatible with a broad range of substituents in the amines or
the o-iodo isothiocyanate. Aliphatic secondary amines (a–c,
Table 2) and primary amines (d, Table 2) were particularly effec-
tive providing an excellent yield of the desired products (1a, 1b,
1c and 1d) through sequential formation of the respective thio-
ureas and subsequent intramolecular arylthiolation. The structure
of the product (1b) has been further confirmed by X-ray crystal-
lographic analysis as shown in Fig. 2. The reaction of 2-iodo-
isothiocyanates (1) with various substituted aryl amines (e–g)
examined also proceeded well to afford the 2-aminobenzothia-
zoles (1e–1g) in good yields (Table 2). Both electron rich (f,
Table 2) and electron deficient (g, Table 2) aromatic amines suc-
cessfully rendered the corresponding benzothiazoles (1f) and
(1g) respectively. Substituted 2-iodo isothiocyanates possessing
electron-donating group (2) and an electron-withdrawing group
(3) with morpholine yielded corresponding thiourea in situ
which were efficiently transformed to their respective benzothia-
zoles (2a) and (3a) in excellent yield under the basic aqueous
medium.
A few notable characteristics of these reactions include the
observation that the reactions were faster for the substrates
thioureas (in situ generated) derived from aliphatic secondary
amines (a–c, Table 2). For primary arylamines having electron-
donating (f) or electron-withdrawing substituents (g) there seem
to be either little or no effect on either reaction time or on the
product yields. A similar result was observed with thioureas
derived from isothiocyanates containing electron-donating (2) or
electron withdrawing substituents (3) (Table 2).
Likewise, when 2-fluoroarylisothiocyanates (Table 4, 10–13)
were treated with various primary and secondary amines, the
resultant o-fluoroaryl thioureas underwent the intramolecular
heteroarylation reaction well in the presence of the catalyst.
However the reaction rate was more sluggish compared to its –I,
–Br or –Cl-analogues. This counts to the high bond energy of
the C–F bond (C–F bond energy 124 kcal mol−1) and attributes
to reluctance of the intramolecular cyclisation. Usually a very
moderate yield of the product was obtained with the o-fluoro
counterpart. This observation further supports our recent obser-
vation that Cu prefers the dehalogenative path over a C–H
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Table 2 Synthesis of 2-aminobenzothiazoles via base-mediated intramolecular arylthiolationa
Substrate
Amine
Productb
Time (h)
Yieldc (%)
a Reactions were monitored by TLC. b Confirmed by IR and 1H and 13C NMR. c Isolated yield.
2494 | Green Chem., 2012, 14, 2491–2498
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being dispersed among the CuO nanoparticles present on the
surface cluster. The intermediate (D) then undergoes an intra-
molecular arylthiolation via a reductive elimination of the catalyst,
which continues the catalytic cycle along with the formation of
the cross coupled product.14,18e
An assessment of the efficacy of the catalyst toward further
catalytic cycles was being performed through a series of reac-
tions involving thiourea derived from 2-chlorophenylisothiocya-
nate (7) and amine (a). In the first cycle 80% conversion
(by G.C.) was obtained after 24 h under the optimised con-
ditions. The product was then extracted out with ethyl acetate
and the aqueous layer containing the dispersed CuO nanoparti-
cles were then subjected to next run by adding thiourea and
K2CO3. In this cycle 75% yield was obtained. This process of
recycling the catalyst was repeated for three more cycles and the
result is summarised in Table 5. The catalyst was found to be
effective up to five cycles giving a conversion up to 73%,
however, with relatively longer reaction time for increasing
cycles.
After five cycles the aqueous layer containing the catalyst was
centrifuged and its morphology was determined by TEM and
powder XRD. A comparative study of the TEM and powder
XRD of the fresh catalyst and the recovered catalyst after five
cycles (Fig. 4 and 5) shows that the catalyst does not undergo
substantial leaching or agglomeration during the recycling
process.
Fig. 2 Ortep view of structure 1b.
Table 3 Optimisation of reaction conditionsa
Entry
Catalyst (mol%)
Base (equiv.)
Time (h)
Yieldb (%)
1
2
3
4
5
6
7
Nil
K2CO3 (3)
K2CO3 (1)
K2CO3 (3)
K2CO3 (2)
K2CO3 (1.5)
K2CO3 (1.5)
K2CO3 (1.5)
24
24
24
24
24
18
16
0
CuO (2)
CuO (2.5)
CuO (2.5)
CuO (2.5)
CuO (5)
CuO (7.5)
68
72
72
72
60
54
a Reactions were monitored by TLC. b Isolated yield.
Conclusion
activation as compared to Pd which prefers mostly C–H
activation for less reactive halogens (–F, –Cl).19 The formation
of dehalogenation product has also been unambiguously estab-
lished by the X-ray crystallography of the product (10q) posses-
sing the chiral amine (Fig. 3). To generalise few observations,
it was found that with both the 2-chloro or the 2-fluoro substi-
tuted thioureas the reactions occurred rather smoothly with the
electron-withdrawing groups on the aryl moiety possessing the
halogen while hardly was there any effect of the substituents on
the aryl amines. However, as with the o-iodo and o-bromo ana-
logues, the reactions with the aliphatic amines were far superior.
The substrates consisting of o-iodo and o-bromo substituents
underwent the cyclisation in the presence of base without the
requirement of metal catalyst (Table 2). Hence, from this obser-
vation, it could be concluded that for iodo and bromo substrates
the reaction proceeded through a base promoted intramolecular
nucleophilic aromatic substitution (INASOB) of o-halothioureas
as has been proposed by others.16 However, the possibility
of a benzyne mechanism for iodo and bromo substrates
could not be ruled out since the halide reactivity follows the
order I > Br > Cl > F when cleavage of C–X bond is the rate
determining step.21 For those containing o-chloro and o-fluoro
the cyclisation was affected by the metal catalyst and there was
no reaction without it. Furthermore, the reaction proceeded
smoothly with an electron-withdrawing group on the aryl moiety
bearing the halide. Hence it is presumed that the mechanistic
path goes via an oxidative addition subsequently followed by a
reductive elimination. CuO nanoparticles (A) bearing highly
reactive morphologies expectedly form an active cluster inter-
mediate (B) which on oxidative addition at the C–X bond may
give intermediate (C) (Scheme 2). The excess positive charge is
In conclusion, we have developed a simple, versatile, efficient on
water one-pot methodology for the synthesis of 2-amino-
benzothiazoles from the in situ generated 2-halothioureas. In the
case of o-iodo and o-bromo substrates, reactions were, in
general, very clean and high yielding without the assistance of
any metal catalyst. However, o-chloro and o-fluoro substrates
undergo intramolecular arylthiolation only in the presence of
CuO nanoparticles. Use of an ecologically favourable base,
recyclable catalyst and water as the reaction medium makes this
methodology a benign alternative to the existing methods.
General procedure
Synthesis of 2-morpholinbenzo[d]thiazole (1a) from 2-iodo
isothiocyanate(1)
2-Iodophenyl isothiocyanate (1) (1 mmol) was treated with mor-
pholine (a) (1 mmol) under neat conditions and immediate for-
mation of the corresponding thiourea was observed. To this
in situ generated thiourea, was subsequently added H2O (5 mL)
and K2CO3 (3 mmol) and the mixture was subjected to reflux in
a preheated oil bath at 100 °C. The progress of the reaction was
monitored by TLC each time by extracting a small aliquot from
the aqueous medium containing dispersed particles using ethyl
acetate. On completion of the reaction (3 h) as judged from TLC
the reaction mixture was cooled to room temperature and
extracted with ethyl acetate (2 × 10 mL). The combined ethyl
acetate layer was dried over anhydrous Na2SO4 and the solvent
was removed under reduced pressure. The crude product was
recrystallised to give the pure product 1a (202 mg, 92% yield).
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Table 4 CuO-nanoparticles catalysed one-pot synthesis of 2-aminobenzothiazolesa
Substrate
Amine
Productb
Time (h)
Yieldc (%)
a Reactions were monitored by TLC. b Confirmed by IR and 1H and 13C NMR. c Isolated yield.
2496 | Green Chem., 2012, 14, 2491–2498
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Fig. 5 Powder X-ray diffraction patterns of (a) fresh CuO nanoparticles
and (b) CuO nanoparticles after fifth cycle.
Fig. 3 ORTEP view of structure 10q.
subsequently added CuO nanoparticles (2.5 mol%), K2CO3
(1.5 mmol) in H2O (5 mL) and the reaction mixture was sub-
jected to reflux in a preheated oil bath at 100 °C. The progress of
the reaction was monitored by TLC each time by extracting
small aliquot of the aqueous medium containing dispersed
particles using ethyl acetate. After 24 h, on completion of the
reaction ( judged by TLC) the reaction mixture was cooled to
room temperature and extracted with ethyl acetate (2 × 10 mL).
The insoluble CuO nanoparticles that remain suspended in the
water can be reused as such for next round of reaction if desired.
The combined ethyl acetate layer was then dried over anhydrous
Na2SO4 and removed under reduced pressure. The crude product
was purified over a column of silica gel eluting with (2 : 8,
EtOAc–petroleum ether) to give the pure product 1a (145 mg,
72% yield).
Scheme 2 Proposed catalytic cycle for intramolecular arylthiolation.
Table 5 Recycling of the catalysta
Acknowledgements
B. K. P. acknowledges the support of this research by the Depart-
ment of Science and Technology (DST) (SR/S1/OC-79/2009),
New Delhi, and the Council of Scientific and Industrial Research
(CSIR) (01(2270)/08/EMR-II). SKR and SG thank CSIR for
fellowships. Thanks are due to Arghya Basu, Himanshu Jena,
Chirantan Kar and Ziyauddin Khan for powder XRD and crystal-
lographic help. Thanks are due to Central Instruments Facility
(CIF) IIT Guwahati for NMR spectra and DST-FIST for XRD
facility.
No of cycle
Conversionb (%)
Time (h)
1
2
3
4
5
80
78
75
73
73
24
25
28
29
31
a Reactions were monitored by TLC. b GC yield.
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Synthesis of 2-morpholinbenzo[d]thiazole (1a) from
2-chloroisothiocyanate (7) using copper nano catalyst
2-Chlorophenyl isothiocyanate (7) (1 mmol) was treated with
morpholine (a) (1 mmol) under neat conditions to provide the
corresponding thiourea. To this in situ generated thiourea, was
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