Studies on spiroheterocycles, Part II: Heterocyclization of the spiro compounds containing cyclohexanone and thiobarbituric acid with different bidentate nucleophilic reagents

Article abstract of DOI:10.1080/00397910600946231

The reaction of thiobarbituric acid with different diarylidene ketones 1a-c yields the spiro compounds 2a-c. The diarylidene derivatives 3a-c are synthesized by the condensation of spiro compounds 2a-c with different aldehydes. A series of spiro heterocyc

Full text of DOI:10.1080/00397910600946231

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Studies on Spiroheterocycles, Part II:
Heterocyclization of the Spiro Compounds
Containing Cyclohexanone and Thiobarbituric
Acid with Different Bidentate Nucleophilic
Reagents
Rajani Kanta Behera a , Ajay Kumar Behera a , Rosy Pradhan a , Anita Pati a
& Manabendra Patra a
a Department of Chemistry, Organic Synthesis Laboratory, Sambalpur
University, Burla, Orissa, India
Available online: 01 Dec 2006
To cite this article: Rajani Kanta Behera, Ajay Kumar Behera, Rosy Pradhan, Anita Pati & Manabendra
Patra (2006): Studies on Spiroheterocycles, Part II: Heterocyclization of the Spiro Compounds Containing
Cyclohexanone and Thiobarbituric Acid with Different Bidentate Nucleophilic Reagents, Synthetic
Communications: An International Journal for Rapid Communication of Synthetic Organic Chemistry, 36:24,
3729-3742
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Synthetic Communicationsw, 36: 3729–3742, 2006
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910600946231
Studies on Spiroheterocycles, Part II:
Heterocyclization of the Spiro Compounds
Containing Cyclohexanone and
Thiobarbituric Acid with Different
Bidentate Nucleophilic Reagents
Rajani Kanta Behera, Ajay Kumar Behera, Rosy Pradhan,
Anita Pati, and Manabendra Patra
Department of Chemistry, Organic Synthesis Laboratory,
Sambalpur University, Burla, Orissa, India
Abstract: The reaction of thiobarbituric acid with different diarylidene ketones 1a–c
yields the spiro compounds 2a–c. The diarylidene derivatives 3a–c are synthesized by
the condensation of spiro compounds 2a–c with different aldehydes. A series of spiro
heterocycles compounds 4a–l, 5a–l, 6a–l, 7a–l, 8a–l, and 9a–l are synthesized from
the diarylidene compounds. The structures of the compounds are ascertained from their
analytical and spectral data. Some of the compounds are screened for their biological
activities.
Keywords: Diarylidene, dibenzal acetone, spiroheterocycles, thiobarbituric acid
INTRODUCTION
In the past few decades, a major motivating force in the synthesis of various
types of organic compounds has been the wide range of biological activities
demonstrated by these compounds. In this sense, spirocyclic and spirohetero-
cyclic compounds in particular provide an intriguing subject for investigation,
because spiro compounds are known to possess various biological activity
Received in India May 8, 2006
Address correspondence to Rajani Kanta Behera, Department of Chemistry,
Organic Synthesis Laboratory, Sambalpur University, Jyoti Vihar, Burla 768 019,
Orissa, India. E-mail: rajanibehera@yahoo.co.in
3729

3730
R. K. Behera et al.
(e.g., fungicidal,[1–4] herbicidal,[5] bactericidal,[6,7] anticonvulsant,[8] anti-
inflammotary,[9] and antianxiety.[10] The derivatives of thiobarbituric acid
and barbituric acid are well known antibacterial agents,[11] sedatives,[12] her-
bicides,[13] fungicides,[14] and antiviral[15] agents. Therefore, the present work
has been undertaken to synthesize a few compounds having spiro centers and
containing biologically active heterocyclic moieties.
RESULTS AND DISCUSSION
The condensation of thiobarbituric acid with dibenzal acetone 1a–c furnished
the spiro compounds 2a–c as illustrated in Scheme 1.
The IR spectra of 2a show two sharp peaks at 1729 and 1678 cm21 for the
two carbonyl stretchings and another absorption band at 3200–3100 cm21 for
N-H stretching. The 1H NMR spectrum of 2a (Ar ¼ C6H5) gives one doublet
0
of doublet centered at d 2.48 (JH8-H 8 ¼ 15 Hz and JH8-H7 ¼ 4 Hz) for the two
0
0
equatorial protons at C-8 and C-10, one triplet at d 3.51 (JH 8-H8 ¼ JH 8-
¼ 15 Hz) for the two axial protons at C-8 and C-10, and another doublet of
H7
0
doublet at d 4.01 (JH7-H 8 ¼ 15 Hz and JH7-H8 ¼ 4 Hz) for two axial protons at
C-7 and C-11. Two broad singlets at d 12.4 and 12.1 correspond to the 2NH
protons. The aromatic protons display a broad multiplet at d 7.11–7.34.
The 13C NMR spectra of this compound gives sharp spikes at d 177.5,
169.8, 168.6, 59.4, 49.9, and 42.2 corresponding to carbonyl adjacent to
nitrogen atoms (C-1 and C-5) and carbonyl adjacent to carbon (C-9), thiocar-
bonyl (C-3), spirocarbon (C-6), 2CH22 (C-8 and C-10), and 2CH2 (C-7
and C-11). Similarly, four peaks, which appeared at d 137.4, 128.8, 128.2,
and 127.8, correspond to the carbon atoms of the phenyl groups.
The spiro compounds 2a–c were condensed with different aromatic
aldehydes in presence of a strong base (i.e., NaOC2H5) to give the diarylidene
compounds 3a–l as illustrated in Scheme 2.
The IR spectrum of 3a (Ar ¼ Ar0 ¼ C6H5) shows the carbonyl absorption
of the cyclohexanone moiety at 1703 cm21. The shift for this carbonyl group
peak from 1729 cm21 to 1703 cm21 may be attributed to conjugation with the
1
exocyclic double bond. The H NMR spectrum of 3a (Ar ¼ Ar0 ¼ C6H5)
Scheme 1.

Synthesis of Macrocyclic Compounds
3731
Scheme 2.
gives two proton singlets at d 3.7 for the two axial protons at C-7 and C-11.
The two doublet of doublet observed in the 1H NMR spectra of 2a
(Ar ¼ C6H5) corresponding to four protons at C-8 and C-10 have disappeared
because of condensation with benzaldehyde at C-8 and C-10. The absence of
the peak at d 49.1 corresponding to CH2 group as observed in case of 2a and
the appearance of a new peak at d 120.0 in the 13C NMR spectrum of 3a
confirm the formation of dibenzylidene compound.
The diarylidene compounds 3a–l on condensation with hydrazine,
phenyl hydrazine, hydroxylamine, urea, guanidine carbonate, and hydrazine
hydrate with acetic acid afforded their respective in situ oxidized products
4–9 respectively (Scheme 3). The driving force for this in situ oxidation is
Scheme 3.

3732
R. K. Behera et al.
the aromatization of the newly built heterocyclic ring similar to the results
reported earlier.[16,17]
The disappearance of the carbonyl stretching frequency at 1703 cm21 in
the IR spectra for 4, 5, 6, and 8 confirm the installation of pyrazole, phenylpyr-
azole, isoxazole, and pyrimidine moieties in 3. In the case of 9a, two peaks at
1705 cm21 and 1659 cm21 in the IR spectrum suggest incorporation of a
2CH3CO group. The IR spectra of 7 show a broad band in the region
3300–3400 cm21 due to an 2OH group. The broad band at 3424 cm21 in
the IR spectrum of 8a may be due to 2NH2.
The 1H NMR spectra of all these compounds 4–9 show complex
multiplets, appearing at d 6.8–7.7 due to the presence of a large number of
aromatic protons along with a singlet in the range of d 3.5–3.7 for the axial
protons of C-7 and C-11.
ANTIMICROBIAL ACTIVITY
Antimicrobial activity was carried out against two pathogenic bacteria,
E. coli and B. cirroflagellosus, and A. niger and Candida albicans as
the fungal strain. The reference drugs used were Norfloxocin and Griseofal-
vin, respectively, with dimethylformamide (DMF) as solvent control. The
cup–plate method[18,19] was used, and nutrient agar was the culture
media. The zone of inhibition frame was measured in millimeters and are
represented by (2), (þ), (þþ), and (þþþ) depending on the diameter
and clarity. Norfloxocin showed a zone of inhibition of 28 mm against
E. coli and 25 mm against B. cirroflagellosus. Griseofalvin exhibited a
zone of 30 mm against both fungi A. niger and C. albicans. The result of
antibacterial and antifungal screening showed that most of the
compounds exhibits weaker or moderate activity (zone of inhibition 12 to
16 mm or 17 to 21 mm) against both bacteria and both fungi as shown in
Table 1.
Experimental, General
The melting points were determined on a Zenith apparatus and are
uncorrected. IR spectra were recorded on a Perkins Elmer FT-IR
spectrophotometer using KBr disc, and 1H NMR were recorded on a
Brucker AC 250-MHz NMR spectrometer and were obtained in CDCl3
unless otherwise stated. Purity of the products was checked by thin-layer
chromatography (TLC), using silica gel ‘G’ (BDH) and hexane-ethylacetate
as eluent.
Dibenzalacetone[20] 1a, 4,40-dianisalacetone[21] 1b, and 4,40-dichlorben-
zalacetone[22] 1c were prepared according to the reported procedure.

Synthesis of Macrocyclic Compounds
3733
Table 1. Antibacterial and antifungal activities of some compounds, 2–9
Zone of inhibition
Comp. no.
E. coli
B. cirroflagellosua
A. niger
C. albicaus
2c
3c
3d
3g
3h
3i
þþ
þþ
þþ
þþ
þ
þþ
þþ
þ
þþ
þ
þþ
þ
þþ
þþ
þþ
þþ
þ
þþ
þ
þþ
þþ
þþþ
þ
þ
þþ
þþ
þþþ
þþ
þþ
þ
þ
3j
þþ
þþ
þþ
þþ
þ
3k
3l
þþ
þþ
þþ
þþ
þþ
þþ
þþþ
þþ
þþ
þþ
þþ
þþ
þþ
þþþ
þ
þþ
þþþ
þþ
þ
4a
4b
4c
4g
4k
4l
þþþ
þþþ
þþþ
þþ
þþþ
þþ
þþ
þþ
þþ
þþþ
þ
þþ
þþ
þþ
þ
þþ
þþ
þþ
þ
5b
5c
5e
5g
5j
þ
þ
þþþ
þ
þ
þ
þþ
þþ
þþ
þþ
þþ
þþ
þþ
þþ
þþ
þþþ
þ
þþ
þþ
þþþ
þ
5k
5l
6c
6e
6g
6i
þþ
þþ
þþ
þþ
þþ
þþþ
þ
þþ
þþ
þþ
þþ
þþ
þþþ
þ
þþ
þ
þþ
þþ
þþ
þþþ
þ
6j
6k
6l
7b
7c
7g
7i
þþ
þþ
þþ
þþ
þþ
þþ
þ
þþ
þþ
þþ
þ
þ
þ
þþ
þþ
þ
þþ
þþ
þþ
þþ
þþ
þ
7j
þþ
þþ
þ
þþ
þþ
þþ
þþ
þ
7k
8b
8c
8g
9b
9c
9e
þþ
þþ
þ
þþ
þþ
þ
þþ
þ
þ
þ
þþ
þ
þþ
þ
þþ
þþ
þþ
þþ
(continued)

3734
R. K. Behera et al.
Table 1. Continued
Zone of inhibition
B. cirroflagellosua A. niger
Comp. no.
E. coli
C. albicaus
9g
9j
þþ
þþ
þþ
þþ
þþ
þþ
þþ
þþ
þþ
þþ
9k
þþþ
þþþ
Notes. (þ) ¼ weakly active (12–16 mm), (þþ) ¼ moderately active (17–21 mm),
and (þþþ) ¼ highly active (22–30 mm).
Synthesis of 7,11-Diphenyl-3-thioxo-2,4-diaza-spiro[5,5]undecane-
1,5,9-trione (2a)
To a solution of thiobarbituric acid (1.44 g, 0.01 mol) in 1,4-dioxane (30 ml)
and dibenzal acetone 1a (2.34 g, 0.01 mole) in ethanol (30 ml), 10 drops of
triethanolamine were added. It was refluxed with stirring for 7 h. The
reaction mixture was filtered, cooled, and poured into ice-cold water. The
obtained solid was filtered, dried, and crystallized from acetic acid. Yield
3.2 g (85%), mp 2488C, anal. calc. for C21H18O3N2S: C, 66.47; H, 4.76; N,
7.40; S, 8.46%. Found: C, 66.32; H, 4.52; N, 7.32; S, 8.38%. IR: 3132 cm21
(2NH), 1708, 1678 cm21 (C55O), 1238 cm21 (C55S); 1H NMR: (d6 DMSO)
d 2.48 (dd, J ¼ 15 Hz, 4 Hz, 2H, 8H/10H equatorial), 3.51 (t, J ¼ 15 Hz,
2H, 8H/10H axial), 4.01 (dd, J ¼ 15 Hz, 4 Hz, 2H, 7H/11H axial), 7.11–
7.34 (m, 10 Ar-H) 12.4 (bs, 1H, NH), 12.1 (bs, 1H, NH); 13C NMR: (d6
DMSO) d 42.2, 49.9, 59.4, 127.8, 128.2, 128.8, 137.4, 168.6, 169.8, 177.5.
Synthesis of 8,10-Dibenzylidene-7-11-diphenyl-3-thioxo-2,4-
diazaspiro[5,5]undecane-1,5,9-triones (3a)
A mixture of 2a (0.378 g, 0.001 mol), NaOC2H5 (0.002 mol) in ethanol
(10 ml) and benzaldehyde (0.21 g, 0.002 mol) was refluxed for 16 h. The
reaction mixture was filtered while hot and acidified with dil. HCl after
cooling. The solid thus separated was filtered, washed with cold water,
dried, and crystallized from ethanol. Yield 0.53 g (75%), mp 1628C. Anal.
calcd. for C35H26O3N2S: C, 75.81; H, 4.69; N, 5.05; S, 5.77%. Found: C,
75.76; H, 4.72; N, 5.11; S, 5.82%. IR: 3200 cm21 (NH), 1703 cm21
1
(C55O), 1246 cm21 (C55S); H NMR: (d6 DMSO) d: 3.7 (s, 2H, 7H/11H),
6.9–7.7 (m, 22H, Ar-H and 2 55CH), 12.3 (bs, 1H, NH), 12.0 (bs, 1H,
NH); 13C NMR: (DMSO) d 54.8, 113.4, 120.01, 128.0–132.0 (many
closely spaced peaks), 137.0, 168.6, 169.6, 172.0.

Synthesis of Macrocyclic Compounds
3735
Synthesis of 80-Benzylidene-1,3,5-trihydro-30,50,70triphenyl-2,6-dioxo-
4-thioxo-spiro[pyrimidine-5,60-pyrazolo[3,4-b]cyclohexane] (4a)
To a solution of 3a (0.11 g, 0.0002 mol) and hydrazine hydrate (0.01 g,
0.0002 mol) in ethanol (5 ml), two drop of piperidine were added. The
mixture was refluxed on a water bath for 19 h. The reaction mixture was
concentrated, cooled, and poured into ice-cold water. The solid thus
separated was filtered, washed, and crystallized from rectified spirit. Yield
0.08 g (72%), mp 1328C. Anal. calcd. for C35H26O2N4S: C, 74.20; H, 4.59;
N, 9.89; S, 5.63. Found: C, 74.16; H, 4.52; N, 9.81; S, 5.57%. IR:
3400 cm21 (NH) 1678 cm21 (C55O), 1607 cm21 (C55N), 1247 cm21
1
(C55S); H NMR: (d6 DMSO) d: 3.7 (s, 2H, 7H/11H), 6.8–7.1 (m, 21H,
Ar-H and 55CH), 9.8 (bs, 1H, NH), 11.98 (bs, 1H, NH), 12.0 (bs, 1H, NH);
13C NMR: (d6 DMSO) d 54.8, 114.1, 128.0–132.0 (many closely spaced
peaks), 137.0, 196.0.
Synthesis of 80-Benzylidene-1,3,5-trihydro-20,30,50,70-tetraphenyl-
2,6-dioxo-4-thioxo-spiro[pyrimidine -5,60-pyrazolo[3,4-
b]cyclohexane] (5a)
To a solution of 13a (0.11 gm, 0.0002 mol) and phenyl hydrazine hydrate
(0.02 g, 0.0002 mol) in ethanol (5 ml), two drop of piperidine were added.
The mixture was refluxed on a water bath for 16 h. The reaction mixture
was concentrated, cooled, and poured into ice-cold water. The solid thus
separated was filtered, washed, and crystallized from ethanol. Yield 0.09 g
(81%), mp 1228C. Anal. calcd. for C41H30O2N4S: C, 76.63; H, 4.67;
N, 8.72; S, 4.98%. Found: C, 76.58; H, 4.68; N, 8.52; S, 4.89%.
1
IR: 3400 cm21 (NH), 1680 cm21 (C55O), 1248 cm21 (C55S); H NMR: (d6
DMSO): d; 3.7 (s, 2H, 7H/11H), 7.2–7.7 (m, 26H, Ar-H and 55CH), 12.0
(bs, 2H, NH).
Synthesis of 80-Benzylidene-1,3,5-trihydro-30,50,70-triphenyl-2,6-
dioxo-4-thioxo-spiro[pyrimidine-5,60-isoxazole[3, 4-b]cyclohexane]
(6a)
To a mixture of 3a (0.11 g, 0.0002 mol) and hydroxylamine hydrochloride
(0.12 g, 0.0002 mol) in ethanol (5 ml), a few drops of KOH (2%) were
added. The mixture was refluxed on a steam bath for 15 h. The reaction
mixture was concentrated, cooled, and poured into ice-cold water. The solid
thus obtained was filtered, washed with water, and crystallized from
ethanol. Yield 0.062 g (55%), mp 1708C. Anal. calcd. for C35H25O3N3S: C,
74.07; H, 4.40; N, 7.40; S, 5.64%. Found: C, 74.01; H, 4.28; N, 7.42;

3736
R. K. Behera et al.
S, 5.67%. IR: 3390 cm21 (NH), 1675 cm21 (C55O), 1609 cm21 (C55N),
1
1245 cm21 (C55S); H NMR: (d6 DMSO); d 3.6 (s, 2H, 7H/11H), 7.1–7.6
(m, 21H, Ar-H and 55CH), 12.1 (bs, 2H, NH).
Synthesis of 90-Benzylidene-1,3,5-trihydro-20-hydroxy-40,60,80-
triphenyl-2,6-dioxo-4-thioxo-5-spiro[pyrimidine-5,70-pyrimido[5,6-
b]cyclohexane] (7a)
To a mixture of 3a (0.11 g, 0.0002 mol) and urea (0.012 g, 0.0002 mol) in
ethanol (5 ml), five drops of conc. HCl were added. The mixture was
refluxed on a steam bath for 18 h. The reaction mixture was cooled and neu-
tralized with 5% NaOH solution. The solid product was filtered, washed
several times with water, and crystallized from acetic acid. Yield 0.081 g
(73%), mp 1388C. Anal. calcd. for C36H26O3N4S: C, 72.72; H, 4.37;
N, 9.42; S, 5.38%. Found: C, 72.77; H, 4.31; N, 9.34; S, 5.22%. IR: 3300–
3400 cm21(broad) (OH and NH), 1685 cm21 (C55O), 1250 cm21 (C55S);
1H NMR: (d6 DMSO): d: 3.68 (s, 2H, 7H/11H), 6.9–7.4 (m, 21H, Ar-H
and 55CH), 9.2 (bs, 1H, OH), 12.0 (bs, 1H, NH).
Synthesis of 20-Amino-90-benzylidene-1,3,5-trihydro-40,60,80-
triphenyl-2,6-dioxo-4-thioxo-spiro[pyrimidine-5,70-pyrimido[5,6-
b]cyclohexane] (8a)
To a refluxing solution of 3a (0.11 g, 0.0002 mol) and guanidine carbonate
(0.036 g, 0.0002 mol) in ethanol (5 ml), a few drops of 40% NaOH were
added. The mixture was refluxed for 16 h, cooled, and acidified with dil.
acetic acid. The solid thus found was filtered, washed with water, and crystal-
lized from acetic acid. Yield 0.072 g (64%), mp 1528C. Anal. calcd. for
C36H27O3N5S: C, 72.84; H, 4.55; N, 11.8; S, 5.39%. Found: C, 72.87;
H, 4.48; N, 11.72; S, 5.31%. IR: 3424 cm21 (broad) (NH), 1705 cm21
1
(C55O), 1247 cm21 (C55S); H NMR: (d6 DMSO): d 3.7 (s, 2H, 7H/11H),
6.9–7.3 (m, 21H, Ar-H and 55CH), 8.3 (s, 2H, NH2), 12.0 (bs, 2H, NH).
Synthesis of 20-Aceto-80-benzelidene-1,3,50-trihydro-30,50,70-
triphenyl-2,6-dioxo-4-thioxo-spiro[pyrimidine-5,60-pyrazole[3,4-
b]cyclohexane] (9a)
A solution of 3a (0.11 g, 0.0002 mol) with hydrazine hydrate (0.01 g,
0.0002 mol) in acetic acid was refluxed for 10 h. The reaction mixture was
concentrated, cooled, and poured into ice-cold water. The solution was
filtered, dried, and crystallized from acetic acid. Yield 0.079 g (73%), mp
1508C. Anal. calcd. for C37H28O3N4S: C, 77.16; H, 4.98; N, 7.34; S, 4.19%.

Table 2. Physical and analytical data
Mp
(8C)
Yield
(%)
C % cal.
(found)
H % cal.
(found)
N % cal.
(found)
Comp.
Ar
Ar0
Mol. formula
.
p-OCH3 C6H4
.
p-Cl C6H4
2b
2c
3b
3c
3d
3e
3f
—
—
205
165
120
140
268
172
82
C23H22O5N2S
78
81
66
52
57
58
68
59
72
62
61
74
67
76
59
62
73
66
61
75
62
65
63.01 (62.79)
56.38 (56.21)
72.31 (72.15)
67.41 (67.32)
66.66 (66.34)
72.31 (72.18)
69.43 (69.35)
65.00 (64.95)
63.06 (63.02)
67.41 (67.35)
65.00 (64.85)
60.69 (60.58)
58.90 (58.78)
70.93 (70.85)
66.14 (66.08)
64.02 (63.95)
70.93 (70.79)
68.22 (68.14)
63.88 (63.92)
62.01 (61.96)
66.14 (66.02)
63.88 (63.72)
5.02 (4.89)
3.58 (3.49)
4.88 (4.92)
3.85 (3.93)
3.80 (3.98)
4.88 (4.73)
5.04 (4.98)
4.09 (4.19)
3.97 (4.11)
3.85 (3.78)
4.09 (4.02)
3.17 (3.12)
3.08 (3.18)
4.79 (4.85)
3.78 (3.58)
3.66 (3.78)
4.79 (4.86)
4.96 (4.83)
4.03 (4.21)
3.91 (3.98)
3.78 (3.69)
4.03 (4.18)
6.39 (6.32)
6.26 (6.30)
4.56 (4.32)
4.49 (4.46)
6.66 (6.52)
4.56 (4.62)
4.15 (4.02)
4.09 (4.21)
7.95 (7.63)
4.49 (4.62)
4.09 (4.11)
4.04 (3.99)
7.85 (7.62)
8.95 (8.68)
8.82 (8.65)
12.80 (12.66)
8.95 (8.88)
8.16 (8.02)
8.06 (8.01)
11.73 (11.65)
8.82 (8.76)
8.06 (8.15)
C21H16O3N2SCl2
C37H30 O5 N2S
C35H24O3N2SCl2
C35H24O7N4S
.
p-OCH3 C6H4
.
p-Cl C6H4
.
p-NO2 C6H4
C6H5
C6H5
C6H5
.
p-OCH3 C6H4
C6H5
p-OCH3 C6H4
C37H30O5N2S
C39H34O7N2S
.
.
p-OCH3 C6H4
.
.
p-Cl C6H4
.
p-NO2 C6H4
3g
3h
3i
p-OCH3 C6H4
95
C37H28O5N2SCl2
C37H28O9N4S
.
p-OCH3 C6H4
262
135
110
121
256
135
125
261
163
141
115
235
117
118
.
p-Cl C6H4
C6H5
p-OCH3 C6H4
C35H24O3N2SCl2
C37H28O5N2SCl2
C35H22O3N2SCl4
C35H22O7N4SCl2
C37H30O4N4S
.
.
3j
p-Cl C6H4
.
.
p-Cl C6H4
3k
3l
p-Cl C6H4
.
p-Cl C6H4
.
p-NO2 C6H4
.
p-OCH3 C6H4
.
p-Cl C6H4
.
p-NO2 C6H4
4b
4c
4d
4e
4f
C6H5
C6H5
C6H5
C35H24O2N4SCl2
C35H24O6N6S
C37H30O4N4S
.
p-OCH3 C6H4
C6H5
p-OCH3 C6H4
.
.
p-OCH3 C6H4
C39H34O6N4S
C37H28O4N4SCl2
C37H28O8N6S
.
.
p-Cl C6H4
.
p-NO2 C6H4
4g
4h
4i
p-OCH3 C6H4
.
p-OCH3 C6H4
.
p-Cl C6H4
C6H5
p-OCH3 C6H4
C35H24O2N4SCl2
C37H28O4N4SCl2
.
p-Cl C6H4
.
4j
(continued)

Table 2. Continued
Mp
(8C)
Yield
(%)
C % cal.
(found)
H % cal.
(found)
N % cal.
(found)
Comp.
Ar
p-Cl C6H4
Ar0
Mol. formula
.
.
p-Cl C6H4
4k
4l
155
266
115
80
C35H22O2N4SCl4
C35H22O6N6SCl2
C43H34O4N4S
78
62
53
62
61
57
76
58
72
53
74
63
58
58
65
76
59
67
68
73
55
72
66
49
59.83 (59.71)
58.01 (57.88)
73.50 (73.39)
69.19 (69.04)
67.21 (67.13)
73.50 (73.41)
70.86 (70.69)
66.92 (66.59)
65.15 (65.01)
69.19 (69.05)
66.92 (66.69)
63.07 (62.91)
61.42 (61.25)
70.81 (70.67)
66.04 (65.91)
63.93 (63.79)
70.81 (70.72)
68.12 (67.98)
63.79 (63.68)
61.92 (61.79)
67.27 (67.08)
63.79 (63.85)
59.57 (59.43)
57.85 (57.68)
3.13 (3.41)
3.04 (2.93)
4.84 (4.93)
3.93 (3.98)
3.82 (3.75)
4.84 (5.02)
4.98 (5.06)
4.15 (4.31)
4.04 (4.21)
3.93 (4.11)
4.15 (4.23)
3.33 (3.46)
3.24 (3.42)
4.63 (4.82)
3.62 (3.87)
3.50 (3.62)
4.63 (4.81)
4.80 (4.93)
3.88 (3.65)
3.77 (3.89)
3.48 (3.65)
3.88 (4.02)
2.98 (3.14)
2.89 (3.02)
7.98 (7.76)
11.60 (11.47)
7.97 (7.85)
7.87 (7.72)
11.47 (11.37)
7.97 (7.82)
7.34 (7.21)
7.26 (7.17)
10.60 (10.52)
7.87 (7.67)
7.26 (7.13)
7.17 (7.12)
10.48 (10.29)
6.70 (6.59)
6.60 (6.49)
10.65 (10.38)
6.70 (6.59)
6.11 (6.03)
6.03 (5.89)
9.76 (9.63)
6.36 (6.48)
6.03 (5.82)
5.96 (5.81)
9.64 (9.86)
.
p-Cl C6H4
.
p-NO2 C6H4
.
p-OCH3 C6H4
.
p-Cl C6H4
.
p-NO2 C6H4
5b
5c
5d
5e
5f
C6H5
C6H5
C6H5
C41H28O2N4SCl2
C41H28O6N6S
C43H34O4N4S
124
136
105
135
124
105
76
.
p-OCH3 C6H4
C6H5
p-OCH3 C6H4
.
.
p-OCH3 C6H4
C45H38O6 N4S
C43H32O4N4SCl2
C43H32O8N6S
.
.
p-Cl C6H4
.
p-NO2 C6H4
5g
5h
5i
p-OCH3 C6H4
.
p-OCH3 C6H4
.
p-Cl C6H4
C6H5
p-OCH3 C6H4
C41H28O2N4SCl2
C43H32O4N4SCl2
C41H26O2N4SCl4
C41H26O6N6SCl2
C37H29O5 N3S
C35H23O3N3SCl2
C35H23O7N5S
.
.
5j
p-Cl C6H4
.
.
p-Cl C6H4
.
p-NO2 C6H4
.
p-OCH3 C6H4
.
p-Cl C6H4
5k
5l
p-Cl C6H4
92
.
p-Cl C6H4
112
165
160
259
90
6b
6c
6d
6e
6f
C6H5
C6H5
C6H5
.
p-NO2 C6H4
.
p-OCH3 C6H4
C6H5
p-OCH3 C6H4
C37H29O5N3S
C39H33O7N3S
.
.
p-OCH3 C6H4
85
.
.
p-Cl C6H4
.
p-NO2 C6H4
6g
6h
6i
p-OCH3 C6H4
162
212
128
117
142
264
C37H27O5N3SCl2
C37H27O9N5S
.
p-OCH3 C6H4
.
p-Cl C6H4
C6H5
p-OCH3 C6H4
C35H23O3N3SCl2
C37H27O5N3SCl2
C35H21O.3N3SCl4
C35H23O7N5SCl2
.
.
6j
p-Cl C6H4
.
.
p-Cl C6H4
.
p-NO2 C6H4
6k
6l
p-Cl C6H4
.
p-Cl C6H4

.
p-OCH3 C6H4
.
p-Cl C6H4
.
p-NO2 C6H4
7b
7c
7d
7e
7f
C6H5
C6H5
C6H5
112
112
258
121
115
135
225
120
142
150
251
128
157
260
183
152
158
248
162
152
193
249
125
145
162
122
C38H30O5N4S
68
57
62
52
48
53
72
55
68
61
51
57
61
65
59
47
74
78
53
68
64
59
59
47
74
78
69.72 (69.58)
65.16 (65.03)
63.16 (63.03)
69.72 (69.59)
67.23 (67.11)
63.07 (62.95)
61.29 (61.17)
65.16 (65.02)
63.07 (62.86)
59.02 (58.83)
57.37 (57.21)
69.83 (69.68)
65.26 (65.13)
63.25 (63.12)
69.83 (69.70)
67.32 (67.14)
63.16 (63.03)
61.37 (61.48)
65.26 (65.17)
63.16 (63.03)
59.10 (58.97)
57.45 (57.38)
70.06 (69.92)
65.58 (65.43)
63.61 (63.48)
70.06 (69.89)
4.59 (4.72)
3.62 (3.59)
3.51 (3.43)
4.59 (4.69)
4.76 (4.58)
3.87 (4.02)
3.76 (3.83)
3.62 (3.79)
3.87 (3.98)
3.01 (3.18)
2.92 (3.08)
4.75 (4.63)
3.78 (3.92)
3.66 (3.87)
4.75 (4.81)
4.91 (5.03)
4.02 (4.16)
3.90 (4.02)
3.78 (3.93)
4.02 (4.19)
3.15 (3.33)
3.06 (2.98)
4.79 (4.83)
3.84 (3.91)
3.72 (3.98)
4.79 (4.86)
8.56 (8.39)
8.45 (8.62)
C36H24O3N4SCl2
C36H24O7N6S
C38H30O5N4S
12.28 (12.11)
8.56 (8.46)
7.84 (7.92)
.
p-OCH3 C6H4
C6H5
p-OCH3 C6H4
.
.
p-OCH3 C6H4
C40H34O7N4S
C38H28O5N4SCl2
C38H28O9N6S
.
.
p-Cl C6H4
.
p-NO2 C6H4
7g
7h
7i
p-OCH3 C6H4
.
p-OCH3 C6H4
7.75 (7.89)
11.29 (11.21)
8.45 (8.320
7.75 (7.52)
.
p-Cl C6H4
C6H5
p-OCH3 C6H4
C36H24O3N4SCl2
C38H28O5N4SCl2
C36H22O3N4SCl4
C36H22O7N6SCl2
C38H31O4N5S
.
.
7j
p-Cl C6H4
.
.
p-Cl C6H4
.
p-NO2 C6H4
.
p-OCH3 C6H4
.
p-Cl C6H4
7k
7l
p-Cl C6H4
7.65 (7.53)
.
p-Cl C6H4
11.16 (11.32)
10.72 (10.63)
10.57 (40.39)
14.35 (14.22)
10.72 (10.59)
9.82 (9.71)
8b
8c
8d
8e
8f
C6H5
C6H5
C6H5
C36H25O2N5SCl2
C36H25O6N7S
C38H31O4N5S
.
p-NO2 C6H4
.
p-OCH3 C6H4
C6H5
p-OCH3 C6H4
.
.
p-OCH3 C6H4
C40H35O6N5S
C38H29O4N5SCl2
C38H29O8N7S
.
.
p-Cl C6H4
.
p-NO2 C6H4
8g
8h
8i
p-OCH3 C6H4
.
p-OCH3 C6H4
9.70 (9.65)
13.19 (13.03)
10.57 (10.42)
9.70 (9.81)
.
p-Cl C6H4
C6H5
p-OCH3 C6H4
C36H25O2N5SCl2
C38H29O4N5SCl2
C36H23O2N5SCl4
C36H23O6N7SCl2
C39H32O5N4S
.
.
8j
p-Cl C6H4
.
.
p-Cl C6H4
.
p-NO2 C6H4
.
p-OCH3 C6H4
.
p-Cl C6H4
.
p-NO2 C6H4
C6H5
8k
8l
p-Cl C6H4
9.58 (9.47)
.
p-Cl C6H4
13.03 (12.89)
8.38 (8.21)
8.27 (8.11)
9b
9c
9d
9e
C6H5
C6H5
C6H5
C37H26O3N4SCl2
C37H26O7N6S
C39H32O5N4S
12.03 (11.93)
8.38 (8.27)
.
p-OCH3 C6H4
(continued)

Table 2. Continued
Mp
(8C)
Yield
(%)
C % cal.
(found)
H % cal.
(found)
N % cal.
(found)
Comp.
Ar
Ar0
Mol. formula
.
.
p-OCH3 C6H4
.
p-Cl C6H4
.
p-NO2 C6H4
9f
9g
9h
9i
p-OCH3 C6H4
112
142
221
115
135
162
240
C41H36O7N4S
C39H30O5N4SCl2
C39H30O9N6S
53
74
78
53
68
52
58
67.58 (67.39)
63.50 (63.38)
61.74 (61.58)
65.58 (65.43)
63.50 (63.39)
59.52 (59.38)
57.89 (57.73)
4.95 (5.03)
4.07 (4.19)
3.96 (4.05)
3.84 (4.08)
4.07 (4.15)
3.22 (3.03)
3.13 (3.28)
7.69 (7.51)
7.60 (7.49)
11.08 (10.94)
8.27 (8.19)
7.60 (7.52)
7.51 (7.43)
10.95 (10.83)
.
p-OCH3 C6H4
.
p-OCH3 C6H4
.
p-Cl C6H4
C6H5
p-OCH3 C6H4
C37H26O3N4SCl2
C39H30O5N4SCl2
C37H24O3N4SCl4
C37H24O7N6SCl2
.
.
9j
9k
9l
p-Cl C6H4
.
.
p-Cl C6H4
.
p-NO2 C6H4
p-Cl C6H4
.
p-Cl C6H4

Synthesis of Macrocyclic Compounds
3741
Found: C, 73.02; H, 4.60; N, 9.21; S, 5.26%. IR: 3400 cm21 (NH), 2928 cm21
(OH), 1705 cm21, 1659 cm21 (C55O), 1609 cm21 (C55N), 1248 cm21
1
(C55S); H NMR: (d6 DMSO): d 2.5 (s, 3H, CH3CO 2 ), 3.68 (s, 2H, 7H/
11H), 6.9–7.4 (m, 21H, Ar-H, 55CH), 12.1 (bs, 2H, NH).
The synthesis of all other derivatives such as 2b–c, 3b–l, 4b–l, 5b–l,
6b–l, 7b–l, 8b–l, and 9b–l has been done as per the detailed procedure
presented under the representative compounds and their physical and analyti-
cal data have been furnished in Table 2.
ACKNOWLEDGMENT
The authors thank the Department of Science and Technology, government of
India, and University Grant Commission, New Delhi, for FIST and DRS
support.
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