Arylthioureas with bromine or its equivalents gives no 'Hugerschoff' reaction product

Article abstract of DOI:10.1039/c003892j

The in situ generated aryl-alkyl unsymmetrical thiourea obtained by the reaction of an aryl isothiocyanate with an aliphatic secondary amine on treatment with bromine or its equivalent gave exclusively a product having a thioamido guanidino moiety and not the expected Hugerschoff product 2-aminobenzothiazole. A plausible reaction mechanism has been proposed for this unprecedented transformation and the scope has been extended to various substrates. The Royal Society of Chemistry 2010.

Full text of DOI:10.1039/c003892j

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www.rsc.org/obc | Organic & Biomolecular Chemistry
Arylthioureas with bromine or its equivalents gives no ‘Hugerschoff’ reaction
product†
Ramesh Yella, Siva Murru, Abdur Rezzak Ali and Bhisma K. Patel*
Received 5th March 2010, Accepted 27th May 2010
First published as an Advance Article on the web 16th June 2010
DOI: 10.1039/c003892j
The in situ generated aryl–alkyl unsymmetrical thiourea
obtained by the reaction of an aryl isothiocyanate with an
aliphatic secondary amine on treatment with bromine or its
equivalent gave exclusively a product having a thioamido
guanidino moiety and not the expected Hugerschoff product
2-aminobenzothiazole. A plausible reaction mechanism has
Scheme 1 Reaction products of the in situ generated thiourea with
EDPBT.
been proposed for this unprecedented transformation and the
scope has been extended to various substrates.
Table 1 Reagent dependent reactivity of phenyl isothiocyanate and
piperidine in CH2Cl2
Introduction
Total isolated yield Ratio aof
The classical Hugerschoff reaction known since 1901 involves the
reaction of a 1,3-diaryl thiourea and liquid bromine in chloroform
medium to produce 2-aminobenzothiazole.1 This reaction essen-
tially involves the intramolecular aromatic electrophilic substitu-
tion reaction of an aryl ring to the thiocarbonyl group of a thiourea
and the process is facilitated by thiophilic bromine. Subsequently,
the same has been achieved with bromine equivalents such as
Entry Brominating Reagent/time
of (1a) +(1a¢)
(1a): (1a¢)
1
2
3
4
5
6
EDPBT/0.5 h
89
86
78
85
80
75
77 : 12
70 : 16
48 : 30
68 : 17
73 : 7
Bu4N+Br3-/0.5 h
[Bmimb]+Br3-/1 h
PhCH2N+Me3Br3-/1 h
CH3(CH2)15N+Me3Br3-/3 h
Br2/1 h
40 : 35
benzyltrimethylammonium tribromide,2 and [Bmim]Br3 in an
3
a Isolated yields. b Bmim = 1-butyl-3-methylimidazolium.
ionic liquid in a controlled manner and is reported to give better
yield with fewer side products. Irrespective of the reagents, Br2 or
its equivalents used, 1,3-diarylthiourea or aryl–alkylthioureas are
reported to give 2-aminobenzothiazole as the major product. This
is true even when one side of the thiourea is an arylamine and the
other a secondary alkyl amine such as pyrrolidine or piperidine.2,3
reagent. We have been working on various bromine equiva-
lents such as tetrabutylammonium tribromide (TBATB),6 and
EDPBT4,5,7 for last decade. All these reagents are after all bromine-
less brominating reagent with similar reactivity hence we have
never encountered any major change in their reactivity/selectivity.
Thus, there is no reason why the product obtained using different
brominating reagents should be so much different. In order to
ascertain this, the same reaction was performed in CH2Cl2 with
different brominating reagents including bromine and the result is
summarised in Table 1.
As can be seen from Table 1, irrespective of the brominating
reagent used, the formation of the product containing a thioamido
guanidino moiety (1a) is always the dominant over the expected 2-
aminobenzothiazole (1a’). The difference in distribution of two
products with various brominating reagents listed in Table 1
could possibly be due to the intrinsic acidity caused by these
reagents in the reaction medium. Acidity is dependent on the
nature of the reagent i.e. counter cation present in a given
solvent. It may be mentioned here that in a classical Huger-
schoff reaction the substrates employed are 1,3-diarylthioureas,
where the arylamines are primary and not secondary in nature.
These kind of substrates invariably gives Hugerschoff product
2-aminobenzothiazole irrespective of the nature of brominating
reagents used. However the difference is noticed only when
one side of the thiourea is having a primary arylamine and
the other side a secondary aliphatic amine. Thus, in the latter
case irrespective of the brominating reagent (Table 1) used the
Results and discussion
In one of our ongoing projects, we treated phenyl isothiocyanate
(1), (1 equiv.) and piperidine (a), (1 equiv.) in CH2Cl2 to which
was added bromine equivalent, 1,2-dipyridiniumditribromide-
ethane (DPTBE)4/[1,1¢(ethane-1,2-diyl)dipyridinium bistribro-
mide (EDPBT)],5 a ditribromide reagent, and stirred for 1 h. The
major product isolated (77%) was found to have a thioamido
guanidino moiety (1a) and the minor product (~12%) was the
expected 2-aminobenzothiazole (1a’) as shown in Scheme 1. This
observation was consistent even when the reaction was carried out
with an isolated thiourea as shown in Scheme 1.
This result however, is in sharp contrast to the recent report
by Jordan2 and Le3 et al. where 2-aminobenzothiazole (1a’) is
reported to be the major product. The only difference between
Jordan,2 Le3 et al. and ours is the selection of the brominating
Indian Institute of Technology Guwahati, Guwahati 781 039, Assam, India.
E-mail: patel@iitg.ernet.in; Fax: +91-361-2690762; Tel: +91-361-2582307
† Electronic supplementary information (ESI) available: 1H and 13C NMR
spectra. CCDC reference numbers 754857–754861. For ESI and crystallo-
graphic data in CIF or other electronic format see DOI: 10.1039/c003892j
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Table 2 Solvent dependency of Hugerschoff reaction with EDPBT
corresponding symmetrical disulfides (K) and (L) respectively.
However, formation of the major product 2e can be explained if
there is formation of a mixed disulfide (M) as shown in Scheme 3.
In principle, the intramolecular attack of the two different imino
nitrogens on to the adjacent imino carbons of the mixed disulfide
(M) is expected to result in two isomeric products. Interestingly,
the formation of only one of the isomeric products was clearly
observed. The structure of the product (2e) has been unequivocally
confirmed by X-ray crystallographic analysis as shown in Fig. 1.8
Total isolated yield of
(1a)+(1a¢)
Entry
Solvent/time
Ratio a(1a):(1a¢)
1
2
3
4
5
6
7
8
CH2Cl2/0.5 h
CH3CN/0.5 h
Dioxane/1.5 hb
THF/1.5 hb
THF/1.5 h
MeOH/0.5 h
DMF/0.5 h
AcOH/0.5 h
89
82
75
92
94
80
78
77
77 : 12
68 : 14
60 : 15
85 : 7
94 : 0c
80 : 0d
78 : 0
55 : 22
a Isolated yields. b Possibly due to lesser solubility of EDPBT reagent.
c Reaction was performed with 0.25 eq. of EDPBT. d Some other minor
side products were also obtained.
anti-Hugerschoff i.e product containing a thiomido guanidino
moiety (1a) is the major product (Table 1). The results of Jordan,2
Le3 et al. even under their reported condition could not be repro-
duced in our hand. We always obtained a thioamido guanidino
moiety (1a) as the major product and 2-aminobenzothiazole (1a’)
as the minor product, where as they have reported the exclusive
formation of 2-aminobenzothiazole under an identical condition.
Next, we wished to investigate the effects of various solvents on
the distribution of products (1a) and (1a’). The above reaction was
performed in various organic solvents listed in Table 2 using 1,1¢-
(ethane-1,2-diyl)dipyridinium bistribromide (EDPBT) in the ratio
of 1 : 0.5 equiv. of the thiourea and EDPBT. Since EDPBT used
here is 0.5 equivalents (being a ditribromide reagent the bromine
content is 1 equivalent). From Table 2, it is evident that irrespective
of the solvents used, the major product is having a thioamido
guanidino moiety (1a). Better selectivity was obtained in THF
compared to other solvents, possibly due to the controlled release
of bromine from EDPBT due to its partial solubility (Table 2,
entry 4). Even using of 0.25 equiv. of EDPBT resulted the exclusive
formation of 1a (Table 2, entry 5).
Fig. 1 ORTEP molecular diagram of 2e.8 H atoms are omitted for clarity.
A mechanism as shown in Scheme 2 can be proposed to account
for the formation of the product (1a). This mechanism essentially
involves the formation of a disulfide intermediate (Z) followed
by the attack of one of the iminium nitrogens on to the adjacent
iminium carbon with the concurrent expulsion of elemental sulfur
to give the desired product (1a) as shown in Scheme 2.
Scheme 3 Crossover experiment and product distribution.
Previously, we have observed a good correlation between pKa’s
of the amines and the regioselective N-acylation of thioureas9a
and also during the formation of 2-imino-4-thiazolidinones.9b
Having the knowledge of pKa’s of the amines7b,7e and reactivity
of the thioureas,9 one can account for the exclusive formation
of the product (2e). Due to the higher pKa of p-methyl aniline
(pKa = 5.08) compared to o-chloro aniline (pKa = 2.65), the
imine nitrogen of the former is expected to be more nucleophilic
and hence preferentially attack in an intramolecular fashion as
shown in Scheme 2 and 3 giving the major product (2e). Further,
due to the lower pKa of o-chloroaniline (pKa = 2.65) its imine
nitrogen preferentially gets protonated over the other imine of the
intermediate (M) there by enhancing the electrophilicity of the
imine carbon of o-chloroaniline as shown in Scheme 3.
The scope of this reaction has been demonstrated with various
aliphatic secondary amines such as piperidine (a), morpholine (b),
pyrrolidine (c) and di-n-butylamine (d) to give major products
(1a), (1b), (1c), and (1d) respectively, all possessing the thioamido
guanidino moiety as shown in Table 3. Structure of the product 1a
has been confirmed by crystal X-ray crystallography as shown
Scheme 2 Proposed mechanism for the formation of (1a).
In order to ascertain this mechanism, a crossover experiment
as shown in Scheme 3 was performed. The in situ generated
thioureas from their corresponding isothiocyanates (2 and 8) and
morpholine (b) on treatment with EDPBT gave three products,
2b, 2e and 8b, isolated in 8%, 78% and 11% yields respectively.
In this reaction, two symmetrical disulfides (K) and (L) and
an unsymmetrical disulfide (M) (Scheme 3) is expected to form
in the medium. Products 2b and 8b can originate from their
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Table 3 Reaction of phenyl isothiocyanates with secondary amines and
Table 4 Reaction of arylisothiocyanates with secondary amines and
DPTBE/EDPBTa
EDPBTa
Isothiocyanate Sec.amine/time/h Productb, yield (%)c
Substrate
Sec. amine/Time/h
% of (X)b,c
% of (Y)b,c
Sub = o-Cl (2)
Sub = o-Cl (2)
Sub = o-Br (3)
Sub = m-NO2 (4)
Sub = p-Cl (5)
Sub = p-Br (6)
Sub = p-Br (6)
Sub = p-CF3 (7)
Sub = p-CF3 (7)
Sub = p-CH3 (8)
Sub = p-OMe (9)
(b)/2 h
(2b)/86%
(2c)/89%
(3b)/85%
(4a)/84%
(5b)/88%
(6a)/83%
(6b)/86%
(7b)/87%
(7c)/86%
(8b)/60%
(9c)/58%
(2b¢;)/nd
(2c¢;)/nd
(3b¢;)/nd
(4a¢;)/nd
(5b¢;)/nd
(6a¢;)/nd
(6b¢;)/nd
(7b¢;)/nd
(7c¢;)/nd
(8b¢;)/28%
(9c¢;)/32%
(c)/2 h
(b)/2 h
(a)/1.5 h
(b)/1.5 h
(a)/1.5 h
(b)/1.5 h
(b)/2.5 h
(c)/2.5 h
(b)/1 h
(c)/1 h
a Reactions were monitored by TLC. b Confirmed by IR, 1H NMR and 13
C
a Reactions were monitored by TLC. b Confirmed by IR, 1H NMR and 13
C
NMR spectroscopy. c Isolated yields. nd = not detected.
NMR. c Isolated yield. d nd = not detected
in Fig. 2.10 In all these cases, the Hugerschoff product 2-
aminobenzothiazole was obtained as a minor products (1a’ or
1c’) as shown in Table 3, or not observed at all.
Table 5 Reaction of activated aryl isothiocyanates with secondary amine
and EDPBTa
Isothiocyanate
Sec. amine/time/h Productb
Yieldsc
Fig. 2 ORTEP molecular diagram of 1a.10 H atoms are omitted for clarity.
The success of this strategy was then applied to various other
aryl isothiocyanates (Table 4). Substrates (2) and (3) containing
weakly deactivating substituents (Cl and Br) in the ortho position
gave 2b, 2c and 3b respectively, as the exclusive products. Aryl
isothiocyanate having a strong electron withdrawing group (-NO2)
(4) in its meta position on reaction with piperidine (a), followed
by treatment with EDPBT gave 4a as the only isolated product.
Further, weakly deactivating substituents (Cl and Br) when present
in the para-position of an isothiocyanates (5 and 6), when reacted
with aliphatic secondary amines such as morpholine (b) and piperi-
dine (a) followed by treatment with EDPBT yielded the thioamido
guanidino moiety containing products 5b, 6a and 6b. The structure
of the products 5b and 6a have been further confirmed by crystal X-
ray crystallography (see supporting informations). Isothiocyanate
(7) containing strongly deactivating substituent (-CF3) in its para
position gave sole products 7b and 7c respectively, when reacted
with a secondary amines morpholine (b) and pyrrolidine (c) under
the identical condition. Even isothiocyanates (8 and 9) having
moderately activating groups (Me and OMe) in its para position
gave no significant amount of benzothiazoles 8b’ and 9c’ and the
dominant product was still the anti-Hugerschoff product 8b and
9c respectively.
a Reactions were monitored by TLC. b Confirmed by IR, 1H NMR and 13
C
NMR spectroscopy. c Isolated yields. d Complete conversion was observed
with in 1 h.
Except isothiocyanates (8 and 9), all other aryl isothiocyanates
listed in Table 4 are either moderately deactivated or strongly
deactivated. Thus, they are expected to be less susceptible towards
intramolecular electrophilic substitution to give Hugerschoff
product 2-aminobenzothiazole and are more likely to yield
the intermolecular nucleophilic substitution product i.e anti-
Hugerschoff product. In order to ascertain this effect, we selected
some activated aryl isothiocyanates (10) and (11) as shown in
Table 5.
Interestingly, morpholine thiourea of isothiocyanate (10) when
reacted with EDPBT gave two inseparable regioisomeric benzoth-
iazoles 10b’ and 10b¢¢; in the ratio of 3 : 2. Surprisingly, when
the secondary amine was changed to pyrrolidine (c), (10c’) was
the lone isolated product. 1-Isothiocyanato napthalene (11), an
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activated fused aromatic substrate, under went intramolecular
electrophilic substitution reaction giving exclusively napthothia-
zoles 11b’ and 11c’ respectively, in good yield.
General experimental procedure
General procedure for the preparation of guanidine (1a)
from phenylisothiocyanate and piperidine (a). To a solution of
phenylisothiocyanate 1 (270 mg, 2 mmol.) in THF (2 mL) was
added drop wise piperidine a (197 mL, 2 mmol), dissolved in
THF (2 mL) at room temperature. Formation of thiourea was
observed within 15 min as judged from TLC. To this was then
added EDPBT (666 mg, 1 mmol.) pinch wise over a period of
10 min. The reaction was kept for stirring at room temperature and
complete conversion to anti-Hugerschoff product was observed
within 1 h as can be judged from TLC and from the disappearance
of the orange colour of EDPBT. After completion of the reaction,
solvent was evaporated and the reaction mixture was admixed with
ethyl acetate (15 mL). The ethyl acetate layer was washed with
a saturated solution of NaHCO3 (5 mL), dried over anhydrous
Na2SO4 and concentrated under reduced pressure. The pure
product was isolated by recrystallisation using ethyl acetate and
hexane (8 : 2). Alternatively, the products can be purified by
passing through a silica gel column (saturated with 1% triethyl
amine) and eluted with hexane : ethylacetate (8 : 2) to give 1a
(345 mg, 85%).
Conclusions
In conclusion, we have demonstrated that some of the activated
and all the deactivated aryl thioureas under the Hugerschoff
reaction condition (bromine or its equivalents) gave a product
having a thioamido guanidino moiety (anti-Hugerschoff product)
as the major product. The formation of anti-Hugerschoff reaction
goes via a disulfide intermediate which has been supported by
a cross-over experiment. Further, we have observed that the
generally expected Hugerschoff product is the major product only
when the aryl ring is sufficiently activated.
Experimental
General remarks
Unless otherwise stated, all reagents were purchased from com-
mercial sources and used without further purification. Reaction
progress was monitored by TLC using Merck silica gel 60 F254
(0.25 mm) with detection by UV or iodine. Chromatography was
performed using Merck silica gel (60–120) mesh size with freshly
distilled solvents. Columns were typically packed as slurry and
equilibrated with the appropriate solvent system prior to use.1H
NMR (400 MHz) and 13C NMR (100 MHz) spectra were recorded
on a Varian FT-400 MHz instrument using TMS as an internal
standard. Data are presented as follows: chemical shift (ppm),
multiplicity (s = singlet, d = doublet, t = triplet, m = multiplet, b
= broad, br s = broad singlet, br m = broad multiplet, coupling
constant J (Hz). Elemental analyses were carried out on a Perkin–
Elmer 2400 automatic carbon, hydrogen, nitrogen and sulfur
analyser. Melting points were recorded on Buchi B-545 melting
point apparatus and are uncorrected. IR spectra were recorded in
KBr or neat on a Nicolet Impact 410 spectrophotometer. Mass
data were obtained with a WATERS MS system, Q-tof premier
and data analyzed using Mass Lynx4.1.
N-Phenyl-N-((E)-(phenylimino)(piperidin-1-yl)methyl)piperidine-
1-carbothioamide (1a)
mp: 186–188 ◦C; 1H NMR (400 MHz, CDCl3): d (ppm) 0.84–1.67
(m, 12H), 2.63–3.82 (m, 8H), 6.90 (t, J = 7.6 Hz, 2H), 7.02–
7.12 (m, 3H), 7.16 (t, J = 8.4 Hz, 2H), 7.26–7.40 (m, 3H); 13C
NMR (100 MHz, CDCl3): d (ppm) 23.6, 24.5, 24.6, 24.9, 47.4,
51.4, 122.1, 122.3, 124.1, 128.4, 129.2, 143.7, 149.7, 150.0, 184.9;
IR (KBr): 2936, 2854, 1632, 1588, 1481, 1454, 1416, 1295, 1261,
1240, 1207, 1028, 989, 903, 749 cm-1; MS (ESI): 407.2222 (MH+).
General procedure for the cross-over experiment
To a solution of o-chloro phenyl isothiocyanate 2 (338 mg,
2 mmol.) and p-methyl phenyl isothiocyanate 8 (298 mg, 2 mmol)
in THF (2 mL) was added drop wise morpholine b (175 mL,
4 mmol), dissolved in THF (2 mL) at room temperature. For-
mation of corresponding thioureas was observed within 15 min
as judged from TLC. To this was then added EDPBT (1332 mg,
2 mmol.) pinch wise over a period of 10 min. The reaction was kept
for stirring at room temperature and complete conversion to anti-
Hugerschoff product was observed within 2 h as can be judged
from TLC and from the disappearance of the orange colour of
EDPBT. After completion of the reaction, solvent was evaporated
and the reaction mixture was admixed with ethyl acetate (15 mL).
The ethyl acetate layer was washed with a saturated solution of
NaHCO3 (15 mL), dried over anhydrous Na2SO4 and concentrated
under reduced pressure. The products were purified through a
column of silica gel (saturated with 1% triethyl amine) and eluted
with (hexane:ethylacetate 8 : 2) to give 2b (38 mg, 8%), 2e (358 mg,
78%), and 8b (48 mg, 11%).
Crystallographic Analysis
Crystal data were collected with Bruker Smart Apex-II CCD
diffractometer using graphite by using graphite-monochromated
˚
Mo-Ka radiation (l = 0.71073 A) at 298 K. Cell parameters
were retrieved using SMART11 software and refined with SAINT11
for all observed reflections. Data reduction was performed
with the SAINT software and corrected for Lorentzian and
polarization effects. Absorption corrections were applied with
the SADABS program.12 The structures were solved by direct
methods implemented in the SHELX-9713 program and refined
by full-matrix least-squares methods on F2. All non-hydrogen
atom positions were located in difference Fourier maps and
refined anisotropically. The hydrogen atoms were placed in their
geometrically generated positions. The crystals were isolated in
rectangular shape from ethyl acetate and hexane mixture at room
temperature.
N -((E)-(2-Chlorophenylimino)(morpholino)methyl)-N -(2-chlo-
rophenyl)morpholine-4-carbothioamide (2b). mp: 157 ◦C; 1H
NMR (400 MHz, CDCl3): d (ppm) 2.50–4.60 (m, 16H), 6.39–7.16
(m, 5H), 7.22–7.68 (m, 3H); 13C NMR (100 MHz, CDCl3): d (ppm)
47.1, 47.5, 50.9, 66.1, 122.8, 123.9, 126.5, 127.3, 128.0, 129.1, 131.0,
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139.7, 145.7, 148.6, 187.2; IR (KBr): 2950, 2894, 2849, 1632, 1580,
1470, 1427, 1401, 1363, 1303, 1272, 1237, 1219, 1206, 1159, 1150,
1119, 1109, 1051, 1031, 999, 953, 876, 757, 750 cm-1; Elemental
analysis: C22H24Cl2N4O2S (479.42): calcd C, 55.12; H, 5.05; N,
11.69; S, 6.69. found: C, 55.18; H, 5.09; N, 11.82; S, 6.75.
and A. H. Land, In Heterocyclic Compounds, R. C. Elderfield, Ed.;
J. Wiley, New York, 1957; Vol.5, Chapter 8, pp 484–721.
2 A. D. Jordan, C. Luo and A. B. Reitz, J. Org. Chem., 2003, 68, 8693.
3 Z-G. Le, J-P. Xu, H-Y. Rao and M. Ying, J. Heterocycl. Chem., 2006,
43, 1123.
4 V. Kavala, S. Naik and B. K. Patel, J. Org. Chem., 2005, 70, 4267.
5 S. Naik, V. Kavala, R. Gopinath and B. K. Patel, Arkivoc, 2006, (xi),
21.
6 (a) R. K. Roy, P. Bagaria, S. Naik, V. Kavala and B. K. Patel, J. Phys.
Chem. A, 2006, 110, 2181; (b) R. K. Roy, V. Usha, B. K. Patel and K.
Hairo, J. Comput. Chem., 2006, 27, 773; (c) V. Kavala and B. K. Patel,
Eur. J. Org. Chem., 2005, 441; (d) S. Naik, V. Kavala, R. Gopinath and
B. K. Patel, Arkivoc, 2006, 119; (e) S. Naik, R. Gopinath, M. Goswami
and B. K. Patel, Org. Biomol. Chem., 2004, 2, 1670; (f) R. Gopinath,
Sk. J. Haque and B. K. Patel, J. Org. Chem., 2002, 67, 5842; (g) S.
Naik, R. Gopinath and B. K. Patel, Tetrahedron Lett., 2001, 42, 7679;
(h) B. K. Patel and R. Gopinath, Org. Lett., 2000, 2, 4177.
7 (a) V. Kavala, S. Murru, G. Das and B. K. Patel, Tetrahedron, 2008, 64,
3960; (b) C. B. Singh, S. Murru, V. Kavala and B. K. Patel, Org. Lett.,
2006, 8, 5397; (c) S. Murru, V. Kavala, C. B. Singh and B. K. Patel,
Tetrahedron Lett., 2007, 48, 1007; (d) C. B. Singh, S. Murru, V. Kavala
and B. K. Patel, J. Chem. Res. (S), 2007, 2007, 136; (e) S. Murru, C. B.
Singh, V. Kavala and B. K. Patel, Tetrahedron, 2008, 64, 1931.
8 Crystallographic data for 2e: C23H27ClN4O2S, crystal dimensions 0.30 ¥
N-((E)-(2-Chlorophenylimino)(morpholino)methyl)-N-p-tolyl-
◦
1
morpholine-4-carbothioamide (2e). mp: 133–134 C; H NMR
(400 MHz, CDCl3): d (ppm) 2.24 (s, 3H), 2.64–3.90 (m, 16H),
6.61 (br s, 1H), 6.83 (t, J = 7.6 Hz, 1H), 7.07 (t, J = 7.6 Hz, 2H),
7.22 (d, J = 8.0 Hz, 2H), 7.29 (d, J = 8.0 Hz, 2H); 13C NMR
(100 MHz, CDCl3): d (ppm) 20.9, 47.1, 50.4, 65.4, 66.3, 120.2,
122.8, 123.5, 125.5, 126.4, 127.1, 129.5, 130.3, 134.8, 140.5, 146.2,
150.7, 186.2; IR (KBr): 2963, 2910, 2851, 1631, 1583, 1475, 1436,
1418, 1360, 1291, 1279, 1235, 1156, 1114, 1076, 1021, 998, 941,
851, 813, 754 cm-1; Elemental analysis: C23H27ClN4O2S (459.00):
calcd C, 60.18; H, 5.93; N, 12.21; S, 6.99. found: C, 60.14; H, 5.98;
N, 12.14; S 7.93.
N-((E)-(p-Tolylimino)(morpholino)methyl)-N-p-tolylmorpholine-
4-carbothioamide (8b)
¯
0.23 ¥ 0.18 mm, Mr = 459.00, triclinic, space group P1, a = 9.0◦83(3),
◦
˚
b = 11.470(4), c = 13.401(4) A,a = 66.049(5) ,b = 83.186(5) ,g =
◦
3
-3
-1
˚
Gummy; 1H NMR (400 MHz, CDCl3) d (ppm) 2.25 (s, 3H), 2.33
(s, 3H), 2.74 - 3.75 (m, 16H), 6.80 (br s, 1H), 6.85 (d, J = 8.0 Hz,
2H), 7.05 (d, J = 8.0 Hz, 2H), 7.08–7.27 (m, 3H); 13C NMR
(100 MHz, CDCl3): d (ppm) 20.8, 20.9, 46.7, 50.6, 65.4, 66.2,
121.2, 121.9, 129.2, 130.2, 131.8, 134.4, 140.2, 146.7, 149.5, 185.2;
IR (KBr): 2963, 2919, 2857, 1632, 1607, 1506, 1472, 1422, 1360,
1296, 1279, 1236, 1160, 1115, 1066, 1034, 1018, 999, 940, 911, 855,
829, 818, 732 cm-1; Elemental analysis: C24H30N4O2S (438.59):
calcd. C, 65.72; H, 6.89; N, 12.77; S, 7.31. found C, 65.68; H, 6.84;
N, 12.81; S, 7.26.
67.231(5) , V = 1175.2(6) A , Z = 2, rc = 1.297 mg m , m = 0.278 mm ,
F(000) = 484, reflection collected/unique = 4785/2683, refinement
method = full-matrix least-squares on F2, final R indices [I > 2s(I)]:
R1 = 0.0458, wR2 = 0.1149, R indices (all data): R1 = 0.0577, wR2 =
0.1234, goodness of fit = 0.851. CCDC-754860 (for 2e) contains the
supplementary crystallographic data for this paper. These data can be
obtained free of charge from The Cambridge Crystallographic Data
Centre via www.ccdc.cam.ac.uk/data_request/cif.
9 (a) C. B. Singh, H. Ghosh, S. Murru and B. K. Patel, J. Org. Chem.,
2008, 73, 2924; (b) R. Yella, H. Ghosh and B. K. Patel, Green Chem.,
2008, 10, 1307.
10 Crystallographic data for 1a: C24H30N4S, crystal dimensions 0.29 ¥
0.21 ¥ 0.17 mm, Mr = 406.58, monoclinic, space group P21/◦c, a =
˚
9.5428(10), b = 10.2273(11), c = 22.766(2) A, a = g = 90.00 , b =
◦
3
-3
-1
˚
Acknowledgements
96.034(6) , V = 2209.6(4) A , Z = 4, rc = 1.222 mg m ,m = 0.164 mm ,
F(000) = 872, reflection collected/unique = 5335/3394, refinement
method = full-matrix least-squares on F2, final R indices [I > 2s(I)]:
R1 = 0.0676, wR2 = 0.1946, R indices (all data): R1 = 0.1001, wR2 =
0.2551, goodness of fit = 1.060. CCDC-754859 (for 1a) contains the
supplementary crystallographic data for this paper. These data can be
obtained free of charge from The Cambridge Crystallographic Data
Centre via www.ccdc.cam.ac.uk/data_request/cif.
B. K. P acknowledges the support of this research by the
Department 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). RY and SM thank the
CSIR for fellowships. Thanks are due to Central Instruments
Facility (CIF) IIT Guwahati for Mass and NMR spectra, and
DST-FIST for XRD facility.
11 SMART, SAINT and XPREP, Siemens Analytical X-ray Instruments
Inc., Madison,Wisconsin, USA, 1995.
12 G. M. Sheldrick, SADABS: Empirical Absorption and Correction Soft-
ware, University of Gottingen, Institut fur Anorganische Chemieder
Universitat, Tammanstrasse 4, D-3400 Gottingen, Germany, 1999–
2003.
References
1 (a) H. Hugerschoff, Ber. Dtsch. Chem. Ges., 1901, 34, 3130; (b) H.
Hugerschoff, Ber. Dtsch. Chem. Ges., 1903, 36, 3121; (c) J. M. Sprague
13 G. M. Sheldrick, SHELXS-97, University of Gottingen, Germany,
1997.
This journal is
The Royal Society of Chemistry 2010
Org. Biomol. Chem., 2010, 8, 3389–3393 | 3393
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