Oxidative desulfurization of disubstituted thioureas using Pb(II) salts and investigation of pKa-dependent regioselective N-acylation

Article abstract of DOI:10.1080/17415990903295686

A highly efficient method for the N-acylation of both symmetrical and unsymmetrical thioureas by the use of lead (II) salts and triethylamine has been achieved. The reaction gives regioselective N-acylated product for unsymmetrical thiourea. For unsymmetrical thiuourea, regioselective N-acylation takes place towards the amine having lower pK_a.A linear correlation between the pK_as of the amines and the regioselective Nacylation is found. Another attractive feature of this transformation is that lead sulfide, which is important to material science, is obtained as a side product (nanocubes of 20 nm).

Full text of DOI:10.1080/17415990903295686

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Journal of Sulfur Chemistry
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Oxidative desulfurization of
disubstituted thioureas using Pb(II)
salts and investigation of pK a-
dependent regioselective N-acylation
Harisadhan Ghosh a , Soumya Sarkar a , Abdur Rezzak Ali a &
Bhisma K. Patel a
a Department of Chemistry, Indian Institute of Technology
Guwahati, Guwahati, Assam, India
Published online: 30 Sep 2009.
To cite this article: Harisadhan Ghosh , Soumya Sarkar , Abdur Rezzak Ali & Bhisma K. Patel (2010):
Oxidative desulfurization of disubstituted thioureas using Pb(II) salts and investigation of pK a-
dependent regioselective N-acylation, Journal of Sulfur Chemistry, 31:1, 1-11
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Journal of Sulfur Chemistry
Vol. 31, No. 1, February 2010, 1–11
Oxidative desulfurization of disubstituted thioureas using Pb(II)
salts and investigation of pKa-dependent regioselective
N-acylation
Harisadhan Ghosh, Soumya Sarkar, Abdur Rezzak Ali and Bhisma K. Patel*
Department of Chemistry, Indian Institute of Technology Guwahati, Guwahati, Assam, India
(Received 12 June 2009; final version received 23 August 2009)
A highly efficient method for the N-acylation of both symmetrical and unsymmetrical thioureas by the use
of lead (II) salts and triethylamine has been achieved. The reaction gives regioselective N-acylated product
for unsymmetrical thiourea. For unsymmetrical thiuourea, regioselective N-acylation takes place towards
the amine having lower pKa. A linear correlation between the pKas of the amines and the regioselective N-
acylation is found. Another attractive feature of this transformation is that lead sulfide, which is important
to material science, is obtained as a side product (nanocubes of 20 nm).
Keywords: thiourea; desulfurization; N-acylation; urea; regioselective
1. Introduction
For the construction of heterocycles, ureasand thioureasare very useful synthons(1). N-Acylureas
have found diverse application in agrochemicals and pharmaceuticals (2). For example, derivatives
of acylurea have been used for various synthetic methodologies (3a–i). The anti-Parkinson agent
cabergoline is an N-acyl urea derivative (4). N-Acylated products can additionally be employed
as interesting semi-crystalline materials and auxiliaries for the preparation of chiral cyclic car-
boxylic acids (5). On the other hand, lead compounds have found diverse application in organic
transformations despite their associated toxicity, and their application has dominated the field of
material science in recent years. Lead sulphide (PbS) nanomaterials, due to their narrow band
gap (0.4–0.9 eV), are semiconductors that possess special optoelectronic properties, which have
a diverse array of application (6). A number of PbS nanomaterials with different morphologies
and structures, such as nanobelts (7), nanoparticles (8), nanorods (9), nanowires (10), nanoflakes
(11) and nanocubes (12), have been synthesized.
N-Acylated ureas can be generated from the corresponding thioureas by several methods.
N-Acylation has been achieved from ureas using acetyl chloride or acids at elevated temperatures,
the reaction of amides with isocyanates or carbodiimides with acids (13). Recently, regioselective
*Corresponding author. Email: patel@iitg.ernet.in
ISSN 1741-5993 print/ISSN 1741-6000 online
© 2010 Taylor & Francis
DOI: 10.1080/17415990903295686
http://www.informaworld.com

2
H. Ghosh et al.
N-acetylation of asymmetrical ureas bearing aryl and alkyl groups has been achieved using
Mn(OAc)3 (14). Our group has also recently reported an efficient method for the regioselec-
tive N-acylation of symmetrical and unsymmetrical ureas using diacetoxyiodobenzene (DIB)
(15). The high cost of the DIB is the main detraction of its use, which ultimately inspired us to
explore a more cost-effective route to these compounds.
2. Results and discussion
Manganese and hypervalent iodine-based reagents are thiophilic in nature and so are lead
compounds. This prompted us to investigate whether lead acetate could serve as an N-acylating
agent for the N-acylation of thioureas. The other objective was to find out the origin of regios-
electivity in the N-acylation of unsymmetrical thioureas. In this article, we have demonstrated
an unprecedented regioselective N-acetylation of 1,3-disubstituted thioureas leading to N-acetyl
ureas with concurrent formation of PbS nanomaterials using Pb(OAc)2 · 3H2O (Scheme 1).
In a typical reaction, one equivalent of 1,3-diphenylthiourea 1, one equivalent of Pb(OAc)2 ·
3H2O and two equivalents of triethylamine were mixed together in acetonitrile and stirred at
room temperature. Complete conversion was observed after 12 h; however, when the reaction
was performed at elevated temperature (60 ◦C) complete conversion was achieved within 2 h.
Progress of the reaction was observed by the appearance of the black colored precipitate of PbS.
The proposed mechanism for the formation of N-acetylated product is shown in Scheme 2.
Formation of the N-acylated product, along with PbS as the byproduct, can be explained with
the help of the mechanism shown in Scheme 2. The sulfur atom of the 1,3-disubstituted thiourea
attacks the thiophilic center Pb(II) of Pb(OAc)2, displacing one of the acetate groups and affording
the intermediate (A). The proton abstraction by triethylamine is from the phenyl side of the
O
H
N
H
N
H
N
N
Pb(OAc)2.3H2O
Et3N, CH3CN
+ PbS
S
O
1
1a
Scheme 1. N-Acylation of urea and formation of PbS nanocrystallite.
OAc
Pb
Pb
OAc
OAc
OAc
S
S
N
H
N
H
N
N
H
(A)
21
Et3N
O
O
N
O
N
N
N
N
H
HN
(C)
(B)
O
+ PbS
OAc
Scheme 2. Proposed mechanism of formation of N-acylurea.

Journal of Sulfur Chemistry
3
1,3-disubstituted thiourea (21), as the pKa of the parent amine aniline (pKa 4.63) attached to one
side of the thiourea is lower in comparison to the cyclohexylamine (pKa 10.66) attached to the
other side (16). Reductive β-elimination of intermediate A with the expulsion of PbS produces
carbodiimide intermediate B. The formation of carbodiimide has been confirmed by recording
the IR spectrum of the crude reaction mixture at approximately 50% conversion (as judged by
TLC).
The size and shapes of PbS particles were examined usingTEM. The shape of the PbS crystallite
was found to be nanocube (Figure 1), and the size was approximately 20 nm.
After formulating a plausible reaction mechanism, we focussed our attention on the scope of
this N-acylation reaction on various thioureas. Symmetrical thioureas 2 and 3 afforded their cor-
responding mono-acylated product in moderate to good yields (Table 1). When an o-disubstituted
thiourea, as in the case of 4, was reacted under identical reaction conditions, no traces of acetylated
product were observed. This is probably due to the steric crowding of the two o-methyl groups.
Other 1,3-diaryl thioureas 5, 6, 7 and 8 gave their corresponding acylated product in good yields.
When the methodology was applied to 1,3-cyclohexyl thiourea 9, no traces of acetylated product
could be detected. This is possibly due to the higher pKa of the cyclohexyl amine compared
with aryl amines (16). As such, the triethylamine base used (pKa 10.78) was not basic enough
to abstract a proton from the cyclohexyl amine (pKa 10.66) of thiourea 9 as demanded by the
mechanism.
Having successfully synthesized a series of N-acylated ureas, we were interested in exploring
the regioselective N-acylation of unsymmetrical thioureas. The larger the difference between
the pKas of the precursor amines in the thioureas, the higher the regioselectivity of N-acylation
observed, with preferential acylation taking place toward the amine possessing the lower pKa.
The attack of the acetate group to an unsymmetrical carbodiimide would lead to the protonation
toward the amine/imine having more basic character (higher pKa), while not affecting the imine
group on the other side. The resultant isourea, as proposed in Scheme 2, would then lead to the
formation of N-acylated product after rearrangement.
The measured pKas of aniline and p-methyl aniline are 4.63 and 5.08, respectively (16).
For unsymmetrical thiourea 10, p-methyl aniline nitrogen is more basic compared with aniline
nitrogen of the carbodiimide intermediate; thus, the former is acylated (40%) compared with the
later (60%) as evident from the 1H NMR.
Figure 1. TEM picture of nanocubical PbS.

4
H. Ghosh et al.
Table 1. N-Acylation of ureas from symmetrical thiourea.
Substrate
Product
Yield %
78
O
H
H
N
H
N
N
N
N
N
N
N
(1)
(2)
(3)
(1a)
(2a)
S
S
S
S
S
O
O
H
N
H
N
H
N
81
O
O
H
N
H
N
H
N
69
(3a)
(4a)
O
O
H
N
H
N
H
N
(4)
0
O
O
H
N
H
N
H
N
(5)
O
(5a)
O
86
O
O
O
O
O
O
O
O
H
N
H
N
H
N
N
(6a)
(7a)
(6)
(7)
83
S
O
O
Cl
Cl
Cl
Cl
H
N
H
N
H
N
N
N
83
52
S
S
O
O
H
N
H
N
H
N
(8)
(8a)
O
O
Br
Br
Br
Br
H
N
H
N
H
N
N
(9)
(9a)
0
S
O
Notes: Reactions were monitored by TLC. Products were confirmed by IR, 1H NMR and 13C NMR and
the yield is isolated yield.
To support our arguments that regioselectivity is largely dependent on the pKas of the amine,
acylation of number of unsymmetrical thioureas was performed (Table 2). The measured pKas
of p-chloro (pKa 4.15), p-bromo (pKa 3.86), o-fluoro (pKa 3.20), o-chloro (pKa 2.65), o-iodo
(pKa 2.60) and o-methoxy (pKa 4.52) anilines are lower than that of aniline (pKa 4.63) (16);
thus, the preferential N-acylation took place toward the p-chloro, p-bromo, o-fluoro, o-chloro,
o-iodo and o-methoxy aniline sides in substrates 11, 12, 13, 14, 15 and 16, giving major products
11b, 12b, 13b, 14b, 15b and 16b, respectively. In substrates 17 and 18 possessing p-methoxy
and 2,4-dimethyl aniline, the measured pKas of the parent amines are 5.34 and 4.88, respectively
(16). These values are higher when compared with aniline; thus, preferential acylation took place
toward these amines to afford regioselective products 17a and 18a, respectively. We found that
the larger the difference between the pKas of the amine attached to the thiourea, the greater the
regioselectivity observed.
The pKa difference and the ratio of regioselectivity are tabulated in Table 3 and shown graphi-
cally in Figure 2. The ratios of regioselectivities were calculated assuming the N-acylation toward

Journal of Sulfur Chemistry
5
Table 2. Regioselective N-acylation of ureas from thioureas.
Substrate
Product b
Yield % / Ratio
O
O
O
O
H
N
H
N
H
H
N
N
N
N
82
(10)
+
S
(60 : 40)
(10a)
(10b)
O
O
H
H
N
H
N
H
N
N
N
N
86
(11)
+
+
S
S
O
(11a)
O
(11b)
Cl
(34 : 66)
Cl
Br
Cl
Br
O
H
O
H
N
H
N
H
N
N
N
N
85
(12)
Br
O
(12b)
O
(32 : 68)
(12a)
O
O
F
F
F
Cl
I
H
H
N
H
N
H
N
N
N
N
78
(20 : 80)
(13)
(14)
+
+
O
S
S
O
(13a)
(13b)
O
O
Cl
Cl
H
N
H
N
H
H
N
N
N
N
79
O
(14a)
O
(14b)
(19 : 81)
O
O
I
I
H
H
N
H
N
H
N
N
N
N
(15)
(16)
+
+
70
(32 : 68)
O
S
S
O
(15a)
(15b)
O
O
O
O
O
H
N
H
N
H
H
N
N
N
N
75
O
(16a)
O
(16b)
(43 : 57)
O
O
H
H
H
N
H
N
N
N
N
N
(17)
O
+
+
75
O
O
S
S
O
O
(55 : 45)
(17a)
(17b)
O
O
H
N
H
N
H
H
N
N
N
N
(18)
91
O
(18b)
O
(18a)
(73 : 27)
Notes: Reactions were monitored by TLC. Products were confirmed by IR, 1H NMR and 13C NMR and the ratio was
determined by 1H NMR.
the aniline nitrogen side as unity and the other side as the ratio of it. A plot of pKa difference of
various substituted aromatic amines with respect to aniline in the x-axis and regioselectivity in
the y-axis shows a linear relationship for most of the substrates examined. A negative value of
pKa difference means the ratio of regioselectivity is less than one and positive value means more
than one (Table 3). A direct correlation between the pKa difference and regioselectivity should
fall on a straight line. From the graph (Figure 2), there seems to be few deviations in cases of 13,
15 and 18 having fluoro, iodo and methyl groups in the o-position. These deviations may be due
to the steric factors of these substituents.
Although the pKa difference between the 2,6-dimethyl aniline (pKa 4.74) and aniline (pKa
4.61) in substrate 19 is small, it gave exclusively regioselective product 19a instead of a mixture
of products. This is presumably due to the steric factor imparted by the two o-substituted
methyl groups. Again, the higher acidic character of the aromatic amine aniline (pKa 4.61) and

6
H. Ghosh et al.
Table 3. Regioselective N-acylation of ureas as a function
of pKa (16).
Thioureas
pKa1–pKa2
Ratio of regioselectivity
10
11
12
13
14
15
16
17
18
(−) 0.45
(+) 0.48
(+) 0.77
(+) 1.43
(+) 1.98
(+) 2.03
(+) 0.11
(−) 0.71
(−) 0.25
1 : 0.66
1 : 1.94
1 : 2.12
1 : 4.00
1 : 4.26
1 : 2.13
1 : 1.32
1 : 0.81
1 : 0.36
Notes: pKa1 = pKa of aniline, pKa2 = pKa of other amine attached
to thiourea.
5
o-Chloro
o-Fluro
4
3
2
1
0
o-Iodo
p-Bromo
p-Chloro
o-Methoxy
p-Methoxy
p-Methyl
o,p-Dimethyl
–1.0
–0.5
0.0
0.5
1.0
1.5
2.0
pKa Difference
Figure 2. Plot of pKa-dependent regioselectivity.
p-bromoaniline (pKa 3.86) compared with aliphatic amines, such as benzylamine (pKa 9.41) and
cyclohexylamine(pKa 10.66), indicatesthattheacylationistowardtheanilineandp-bromoaniline
side of the urea, as shown for substrates 20–22 (Table 4). Thus, the exclusive regioselective
formation of products 20a, 21a and 22a appears to be due to the large difference in their pKas.
After investigating the regioselectivity, we were interested in developing a general method
for the preparation of various other N-acylated ureas form 1,3-disubstituted thioureas. We envi-
sioned that this could be achieved by two different strategies. In the first strategy, an external
acid can be added in large excess so that it can attack on carbodiimide to give the N-acylated
product. This method, while successful, invariably formed N-acetylated product along with the
desired N-acylated product. This reaction goes via carbodiimide intermediate that is attacked by
a nucleophilic acetate anion released from Pb(OAc)2. Thus, in an alternative method, the possible
replacement of the lead salt with a non-nucleophilic counter ion, such as nitrate or chloride, and
supplying the acetate ion/acid externally would form N-acylated ureas. Two lead salts, PbCl2 and
Pb(NO3)2 (Table 5), were tested for this purpose, and the latter was found to be more efficient.
In this strategy, when 1,3-diphenylthiourea (1 equivalent), Pb(NO3)2 (1.5 equivalent), triethy-
lamine (4 equivalent) and acid (2.5 equivalent) were mixed together in acetonitrile and stirred
at an elevated temperature (80 ◦C), complete conversion was achieved within 1 h. The proposed

Journal of Sulfur Chemistry
7
Table 4. Regioselective N-acylation of ureas from thiourea.
Substrate
Product
Yield %
O
H
H
N
H
N
N
N
(19a)
(19)
82
S
O
O
H
N
H
N
H
N
Ph
N
N
N
Ph
(20)
(21)
(20a)
(21a)
65
70
S
S
S
O
O
H
N
H
N
H
N
O
O
H
N
H
N
H
N
(22)
(22a)
70
O
Br
Br
Notes: Reactions were monitored by TLC. Products were confirmed by IR, 1H NMR and 13C NMR.
mechanism for the formation of N-acylated product is presumably similar to that stated earlier.
Here, the added acid attacks the carbodiimide intermediate to afford the N-acylated product.
3. Conclusion
In conclusion, we have reported an efficient method for the synthesis of N-acylated ureas from
1,3-disubstituted thioureas using Pb(OAc)2 · 3H2O or Pb(NO3)2. For the first time, Pb(OAc)2 ·
3H2O has been employed as an acylating agent. We have found a direct correlation between the
regioselectivity and the pKas of the amines: the larger the pKa difference between the amines,
the greater the regioselectivity observed. The concurrent formation of PbS nanocrystallite is also
an attractive feature of this methodology.
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 mesh). NMR spectra
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 analysed 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 N-acylated urea (1a) from thiourea (1)
To a stirred solution of diphenylthiourea 1 (228 mg, 1 mmol) and triethylamine (276 μl, 2 mmol)
in acetonitrile (5 ml), lead acetate trihydrate (379 mg, 1 mmol) was added and the reaction mixture
was heated at 60 ◦C for 2 h. A black colored precipitate of PbS was observed during this period.

8
H. Ghosh et al.
Table 5. N-Acylation of ureas from thiourea using Pb(NO3)2 various acids.
Substrate
Acid
Product
Yield %
CH2-CH3
O
H
N
H
N
H
N
N
N
(1)
(1)
(1c)
66
62
CH3CH2COOH
S
S
S
O
O
CH2(CH2)2-CH3
H
N
H
N
H
N
(1d)
CH3(CH2)3COOH
O
O
H
CH2(CH2)2-CH3
H
N
H
N
N
N
(2)
(2)
(6)
(2d)
65
63
73
CH3(CH2)3COOH
CH3(CH2)8COOH
CH3(CH2)8COOH
O
CH2(CH2)7CH3
O
H
N
H
N
H
N
N
N
(2e)
O
O
S
S
CH2(CH2)7CH3
OMe
OMe
OMe
OMe
OMe
H
H
N
H
N
N
(6e)
O
O
CH2(CH2)9CH3
MeO
N
OMe
OMe
H
H
N
H
N
N
(6)
(6f)
71
CH3(CH2)10COOH
O
O
S
S
S
S
Ph
H
N
H
N
H
N
N
(1)
(1)
(1g)
65
66
PhCOOH
O
O
Ph(p-Me)
H
N
H
N
H
N
N
N
(p-Me)PhCOOH
(1h)
Ph(p-Me)
O
O
H
N
H
N
H
N
(5)
OMe
(p-Me)PhCOOH
(5h)
OMe
63
O
MeO
MeO
Notes: Reactions were monitored by TLC. Products were confirmed by IR, 1H NMR and 13C NMR.
The precipitated PbS was filtered, the organic layer evaporated and the resulting residue was
mixed with ethyl acetate (15 ml). The ethyl acetate layer was washed with water (3 × 5 ml). The
organic layer was dried over anhydrous Na2SO4 and concentrated under reduced pressure to give
product 1a. Compound 1a was recrystallized from a mixture of ethyl acetate:hexane (8:2) to
afford colorless crystals.
4.2. General procedure for the preparation of N-acylurea (1d) from thiourea (1) and
pentanoic acid
To a stirred solution of diphenylthiourea 1 (228 mg, 1 mmol), triethylamine (552 μL, 4 mmol)
and pentanoic acid (255 mg, 2.5 mmol) in acetonitrile (5 ml), lead nitrate (331 mg, 1.5 mmol) was
added, and the reaction mixture was heated at 80 ◦C for 1 h.A black colored precipitate of PbS was
observed during this period. The precipitated PbS was filtered hot and washed with acetonitrile
(2 × 2 ml). The organic layer was evaporated, and the resulting residue was mixed with ethyl

Journal of Sulfur Chemistry
9
Table 6. Spectral and analytical data.
Entry
Spectral data
−
1a (15)
m.p. 100–102 ◦C; 1H NMR (CDCl3): δ 1.98 (s, 3H, CH3), 7.08 (t, 1H, J = 7.2 Hz, Ar H), 7.28
(m, 4H, Ar H), 7.48 (m, 5H, Ar H), 11.44 (br s, 1H, NH). 13C NMR(CDCl3): δ 26.8, 120.3,
−
−
− =
=
124.3, 129.1, 129.2, 129.3, 129.9, 137.8, 139.0, 152.1 (NH
3230 (m), 2857 (w), 1722 (s), 1668 (m), 1602 (m) cm−1. HRMS (ESI): MH+, found 255.2946,
15H15N2O2 requires 255.2957.
m.p. 149–151 ◦C; 1H NMR (CDCl3): δ 2.20 (s, 3H, CH3), 4.05 (s, 3H, CH3), 4.17 (s, 3H, CH3),
C O), 175.2 (C O). IR (KBr):
C
6a
−
−
−
7.08–7.14 (m, 2H, Ar H), 7.20–7.30 (m, 3H, Ar H), 7.45 (m, 1H, Ar H), 7.63 (m, 1H,
Ar H), 8.47 (m, 1H, Ar H), 11.99 (brs, 1H, NH). 13C NMR(CDCl3): δ 25.6, 55.8, 56.0, 110.1,
−
−
− =
C O),
112.1, 119.9, 121.0, 121.2, 123.5, 127.7, 128.0, 130.4, 130.7, 148.7, 151.4, 155.3 (NH
175.3 (C O). IR (KBr): 3133 (w), 1719 (s), 1672 (w), 1531 (m) cm−1. HRMS (ESI): MH+,
found 315.1328, C17H18N2O4 requires 315.3481.
=
22a
1d
m.p. 104–106 ◦C; 1H NMR (CDCl3): δ 1.32 (m, 6H), 1.60 (m, 1H), 1.71 (m, 2H), 1.92 (s, 3H),
−
−
1.95 (m, 1H), 3.70 (m, 1H), 7.11 (d, 2H, J = 8.4 Hz, Ar H), 7.58 (d, 2H, J = 8.4 Hz, Ar H),
9.04 (d, 1H, J = 6 Hz, Ar H). 13CNMR (CDCl3): δ 24.8, 25.7, 26.6, 33.0, 49.6, 122.9, 131.0,
−
− =
C
=
132.9, 138.6, 153.5 (NH
O), 174.1 (C O). IR (KBr): 3316 (w), 1705 (s), 1664 (w), 1510
(m) cm−1. C15H19BrN2O2 (339.23): calcd. C 53.11%, H 5.65%, N 8.26%; found: C 53.14%,
H 5.66%, N 8.23%.
m.p. 73–75 ◦C; 1H NMR (CDCl3): δ 0.83 (t, 3H, J = 7.2 Hz, CH3), 1.23 (m, 2H, CH2), 1.56
−
(m, 2H, CH2), 2.14 (t, 2H, J = 7.2 Hz, CH2), 7.08 (t, 1H, J = 7.2 Hz, Ar H)), 7.24–7.32 (m,
4H, Ar H), 7.44–7.54 (m, 3H, Ar H), 7.55 (m, 2H, Ar H), 11.56 (br s, 1H, NH). 13C NMR
−
−
−
(CDCl3): δ 13.9, 22.2, 26.8, 37.6, 120.3, 124.2, 129.1, 129.2, 129.4, 129.9, 137.9, 138.4, 152.3
−1
− =
(NH
=
C
O), 177.8 (C O). IR (KBr): 3131 (w), 2957 (w), 1721 (s), 1660 (w),1562 (m) cm
.
C18H20N2O2 (296.37): calcd. C 72.95%, H 6.80%, N 9.45%; found: C 72.98%, H 6.72%, N
9.42%.
2d
2e
6e
6f
m.p. 106–108 ◦C; 1H NMR (CDCl3): δ 0.83 (t, 3H, J = 7.2 Hz, CH3), 1.24 (m, 2H, CH2), 1.55
(m, 2H, CH2), 2.16 (t, 2H, J = 7.6 Hz, CH2), 2.29 (s, 3H, CH3), 2.40 (s, 3H, CH3), 7.11 (m,
−
−
−
4H, Ar H), 7.27 (d, 2H, J = 8.0 Hz, Ar H), 7.43 (d, 2H, J = 8.0 Hz, Ar H), 11.47 (br s, 1H,
NH). 13CNMR (100 MHz, CDCl3): δ 13.9, 20.9, 21.4, 22.2, 26.8, 37.5, 120.2, 129.0, 129.6,
=
=
130.5, 133.6, 135.4, 135.8, 139.1, 152.3 (NHC O), 177.9 (C O). IR (KBr): 175 (w), 2959
(m), 1715 (s), 1591 (m) cm−1. C20H24N2O2 (324.43): calcd. C 74.05%, H 7.46%, N 8.63%;
found: C 74.13%, H 7.42%, N 8.60%.
m.p. 86–88 ◦C; g1H NMR (CDCl3): δ 0.87 (t, 3H, J = 7.6 Hz, CH3), 1.22 (m, 12H, 6CH2), 1.56
(m, 2H, CH2), 2.15 (t, 2H, J = 7.2 Hz, CH2), 2.30 (s, 3H, CH3), 2.41 (s, 3H, CH3), 7.11 (m,
−
−
−
4H, Ar H), 7.27 (d, 2H, J = 7.6 Hz, Ar H), 7.43 (d, 2H, J = 8.4 Hz, Ar H), 11.46 (br s,
1H). 13CNMR (CDCl3): δ 14.3, 21.0, 21.4, 22.8, 24.8, 29.1, 29.4, 29.5, 32.0, 34.1, 37.9, 120.2,
=
=
129.1, 129.6, 130.5, 133.6, 135.4, 135.8, 139.2, 152.4 (NHC O), 177.9 (C O). IR (KBr): 3167
(w), 2922 (m), 1721 (s), 589 (m) cm−1. C25H34N2O2 (394.56): calcd. C 76.10%, H 8.69%, N
7.10%; found: C 76.12%, H 8.54%, N 7.17%.
m.p. 104–106 ◦C; 1H NMR (CDCl3): δ 0.86 (t, 3H, J = 7.2 Hz, CH3), 1.22 (m, 12H, 6CH2), 1.55
−
(m, 2H, CH2), 2.12 (m, 2H, CH2), 3.77 (s, 3H, CH3), 3.83 (s, 3H, CH3), 6.83 (m, 2H, Ar H),
−
−
−
−
7.03 (m, 2H, Ar H), 7.21 (m, 1H, Ar H), 7.41 (m, 1H, Ar H), 7.48 (m, 2H, Ar H), 11.44
(br s, 1H, NH). 13CNMR (CDCl3): δ 14.3, 22.8, 24.6, 29.1, 29.4, 29.48, 29.52, 32.0, 36.8,
− =
55.6, 55.9, 112.1, 114.2, 121.3, 121.7, 127.1, 130.7, 131.3, 151.9, 155.5, 156.2 (NH
C O),
178.1 (C O). IR (KBr): 3181 (w), 2923 (m), 1716 (s), 1661 (w), 1603 (m) cm−1. C25H34N2O4
(426.56): calcd. C 70.40%, H 8.03%, N 6.57%; found: C 70.48%, H 7.95%, N 6.53%.
m.p. 108–110 ◦C; H NMR (CDCl3): δ 0.87 (t, 3H, J = 7.2 Hz, CH3), 1.10–1.31 (m, 16H, 8CH2),
1.59 (m, 2H, CH2), 2.12 (m, 2H, CH2), 3.82 (s, 3H, CH3), 3.97 (s, 3H, CH3), 6.90 (m, 2H,
=
−
−
−
−
−
Ar H), 7.03 (m, 3H, Ar H), 7.21 (m, 1H, Ar H), 7.42 (m, 1H, Ar H), 8.26 (m, 1H, Ar H),
11.82 (br s, 1H, NH). 13CNMR (CDCl3): δ 4.3, 22.8, 24.7, 29.14, 29.44, 29.47, 29.55, 29.74,
32.1, 36.9, 110.2, 112.1, 120.2, 121.1, 121.2, 123.5, 127.4, 128.1, 130.6, 130.7, 148.8, 151.7,
− =
=
155.6 (NH
C O), 177.7 (C O). IR (KBr): 3175 (w), 2918 (m), 1716 (s), 1670 (w), 1601
(m) cm−1. C27H38N2O4 (454.61): calcd. C 71.34%, H 8.43%, N 6.16%; found: C 71.33%, H
8.40%, N 6.19%.
m.p. 128–130 ◦C; H NMR (CDCl3): δ 7.13, (t, 1H, J = 7.6 Hz, Ar H), 7.16–7.22 (m, 4H,
1
−
1g
−
−
−
Ar H), 7.23–7.29 (m, 6H, Ar H), 7.35 (t, 2H, J = 8.4 Hz, Ar H), 7.62 (d, 2H, J = 7.6 Hz,
Ar H), 11.41 (br s, 1H, NH). 13C NMR (CDCl3): δ 120.5, 124.4, 128.0, 128.1, 128.4, 128.9,
−
− =
=
129.2, 130.3, 130.6, 135.9, 137.8, 138.7, 152.2 (NH
C O), 174.3 (C O). IR (KBr): 2918
(w), 1704 (s), 1611 (w), 1576 (m) cm−1. C20H16N2O2 (316.36): calcd. C 75.93%, H 5.10%, N,
8.85%; found: C 75.81%, H 5.11%, N, 8.80%.
(Continued)

10 H. Ghosh et al.
Table 6. Continued.
Entry
Spectral data
−
1h
m.p. 135–137 ◦C; 1H NMR (CDCl3): δ 2.40 (s, 3H, CH3), 7.13 (t, 1H, J = 7.2 Hz, Ar H), 7.25
−
−
−
(m, 4H, Ar H), 7.34 (m, 3H, Ar H), 7.63 (d, 2H, J = 8.4 Hz, Ar H), 7.75 (d, 2H, J = 7.6 Hz,
Ar H), 7.99 (m, 2H, Ar H). 13CNMR (CDCl3): δ 21.7, 120.5, 124.6, 126.9, 127.3, 129.2,
−
−
− =
=
129.4, 129.6, 130.4, 132.3, 138.2, 142.5, 144.6, 166.1 (NH
C O), 171.4 (C O). IR (KBr):
2918 (w), 1650 (s), 1524 (m) cm−1. C21H18N2O2 (330.39): calcd. C 76.34%, H 5.49%, N
8.48%; found: C 76.29%, H 5.53%, N 8.45%.
5h
m.p. 137–139 ◦C; 1H NMR (CDCl3): δ 2.26 (s, 3H, CH3), 3.73 (s, 3H, CH3), 3.78 (s, 3H, CH3),
−
−
6.77 (d, 2H, J = 8.8 Hz, Ar H), 6.87 (d, 2H, J = 9.2 Hz, Ar H), 6.99 (d, 2H, J = 8.0 Hz,
−
−
−
Ar H), 7.08 (d, 2H,J = 8.8 Hz, Ar H), 7.18 (d, 2H, J = 8.0 Hz, Ar H), 7.51 (d, 2H,
J = 9.2 Hz, Ar H), 11.28 (brs, 1H, NH). 13CNMR (CDCl3): δ 21.6, 55.6, 114.2, 114.3, 122.1,
−
− =
=
128.4, 128.7, 131.0, 131.2, 131.7, 133.2, 140.9, 152.7, 156.5, 159.2 (NH
C O), 174.4 (C O).
IR (KBr): 3176 (w), 1714 (s), 1648 (m), 1513 (m) cm−1. C23H22N2O4 (390.44): calcd. C
70.75%, H 5.68%, N 7.17%; found: C 70.71%, H 5.72%, N 7.22%.
acetate (15 ml). The ethyl acetate layer was washed with water (3 × 5 ml). The organic layer was
dried over anhydrous Na2SO4 and concentrated under reduced pressure to give crude product 1d.
Pure product was obtained after passing through a short column of silica gel using a mixture of
hexane:ethylacetate (92:8) to furnish the pure product in 62% yield.
4.3. Characterization of compounds
1a, 1c, 2a, 3a, 5a, 8a, 17a, 19a, 20a, 21a (15) and 7a (14) are reported. For those compounds, 1H
NMR, 13C NMR, IR (KBr) and m.p. data have been correlated with the reported one. Regioiso-
meric mixtures were analysed by measuring the integration of N-acyl as well as NH peaks. The
spectral data (1H NMR, 13C NMR, IR (KBr) and HRMS) of the remaining compounds are given
in Table 6.
Acknowledgements
B.K.P. acknowledges the support of this research from DST New Delhi (SR/S1/OC-15/2006 and SR/S5/NM-01/2005)
and CSIR 01(1688)/00/EMR-II. H.G. to CSIR for fellowship. Special thanks to CB and KKS for TEM and CIF IIT
Guwahati for the NMR and mass spectrometry work.
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