Synthesis of some new 2-Oxo-N-[(10H-phenothiazin-10-yl)alkyl] derivatives of azetidine-1-carboxamides

Article abstract of DOI:10.1002/hlca.201100364

The synthesis of a new series of 4-aryl-3-chloro-2-oxo-N-[3-(10H- phenothiazin-10-yl)propyl]azetidine-1-carboxamides, 4a-4m, is described. Phenothiazine on reaction with Cl(CH₂)₃Br at room temperature gave 10-(3-chloropropyl)-10H-phenothiazine (1), and the latter reacted with urea to yield 1-[3-(10H-phenothiazin-10-yl)propyl]urea (2). Further reaction of 2 with several substituted aromatic aldehydes led to N-(arylmethylidene)-N′-[3-(phenothiazin-10-yl)propyl]ureas 3a-3m, which, on treatment with ClCH₂COCl in the presence of Et₃N, furnished the desired racemic trans-2-oxoazetidin-1-carboxamide derivatives 4a-4m. The structures of all new compounds were confirmed by IR, and ¹H- and ¹³C-NMR spectroscopy, FAB mass spectrometry, and chemical methods. Copyright

Full text of DOI:10.1002/hlca.201100364

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Helvetica Chimica Acta – Vol. 95 (2012)
Synthesis of Some New 2-Oxo-N-[(10H-phenothiazin-10-yl)alkyl] Derivatives
of Azetidine-1-carboxamides
by Ritu Sharma*, Pushkal Samadhiya, S. D. Srivastava, and S. K. Srivastava
Synthetic Organic Chemistry Laboratory, Department of Chemistry, Dr. H. S. Gour University
(A Central University); Sagar-470003, India
(phone: þ 91-9907656136; e-mail: ritusharmaic@rediffmail.com)
The synthesis of a new series of 4-aryl-3-chloro-2-oxo-N-[3-(10H-phenothiazin-10-yl)propyl]azeti-
dine-1-carboxamides, 4a – 4m, is described. Phenothiazine on reaction with Cl(CH2)3Br at room
temperature gave 10-(3-chloropropyl)-10H-phenothiazine (1), and the latter reacted with urea to yield 1-
[3-(10H-phenothiazin-10-yl)propyl]urea (2). Further reaction of 2 with several substituted aromatic
aldehydes led to N-(arylmethylidene)-N’-[3-(phenothiazin-10-yl)propyl]ureas 3a – 3m, which, on treat-
ment with ClCH2COCl in the presence of Et3N, furnished the desired racemic trans-2-oxoazetidin-1-
1
carboxamide derivatives 4a – 4m. The structures of all new compounds were confirmed by IR, and H-
and 13C-NMR spectroscopy, FAB mass spectrometry, and chemical methods.
Introduction. – The 2-oxoazetidine skeleton has been recognized as a useful
building block in synthesis of biologically important compounds [1][2]. This is mainly
due to the strain energy associated with the four-membered azetidine ring, which
makes it susceptible for nucleophilic ring cleavage. This factor is also responsible for
their application of azetidines as synthones for various stereoselective syntheses of
biologically active heterocyclic compounds [3]. Recently, several reports have high-
lighted different methodologies for the stereoselective syntheses of b-lactams [4 – 6].
10H-Phenothiazine is also of pharmaceutical importance because of different bio-
logical activities, viz. antibacterial [7], antitubercular [8], and anti-inflammatory
properties [9]. Chemically, phenothiazine has two active sites, C(2) and N(10). Here,
we report on substitution at N(10) of phenothiazine and the combination with the 2-
oxoazetidine ring in a single molecule.
Results and Discussion. – The title compounds were synthesized in four steps as
depicted in the Scheme. 10H-Phenothiazine, on reaction with Cl(CH2)3Br at room
temperature, gave 10-(3-chloropropyl)-10H-phenothiazine (1) [10], which was reacted
with urea at room temperature to yield 1-[3-(10H-phenothiazin-10-yl)propyl]urea (2)
[11]. Compound 2, on further reaction with several substituted aromatic aldehydes,
afforded 1-(arylmethylidene)-3-[3-(10H-phenothiazin-10-yl)propyl]ureas 3a – 3m [12].
The latter, on treatment with ClCH2COCl in the presence of Et3N, furnished the final
products, racemic trans-4-aryl-3-chloro-2-oxo-N-[3-(10H-phenothiazin-10-yl)propyl]-
azetidine-1-carboxamides 4a – 4m [13]. The structures of all the newly synthesized
compounds were confirmed by IR, 1H- and 13C-NMR spectroscopy, FAB-mass
spectrometry, and chemical methods.
ꢀ 2012 Verlag Helvetica Chimica Acta AG, Zꢁrich

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Scheme. Synthesis of Compounds 3a – 3m and 4a – 4m
The characteristic IR absorption for Schiff bases 3a – 3m appeared in the range of
1539 – 1560 cmꢀ1, and, in the 1H- and 13C-NMR spectra, the CH¼N signals appeared in
1
the range of 7.85 – 8.05 and 152.1 – 157.6 ppm, respectively. In the H-NMR spectrum,
the broad signal of NH2 in 2 has disappeared. In the IR spectra of 4a – 4m, the C¼O
group of the b-lactam ring showed a characteristic absorption in the range of 1725 –
1
1746 cmꢀ1, and H-NMR spectra exhibited two doublets for CHN and CHCl in the
range of 5.09 – 5.23 and 4.40 – 4.61 ppm, respectively. The coupling constant J(3,4) of
5.00 – 5.25 Hz in the 1H-NMR spectra of 4a – 4m, clearly indicated the formation of the
trans-diastereoisomer of azetidine [14 – 17]. In the 13C-NMR spectra of 4a – 4m, three
characteristic signals appeared for CHN, CHCl, and CO in the ranges of 60.2 – 65.7,
1
51.6 – 56.7, and 165.7 – 170.7 ppm, respectively. The IR absorption, as well as the H-
and 13C-NMR signals corresponding to the N¼CH moieties have disappeared.
Conclusions. – In the present study, the successful synthesis of compound 3a – 3m
and 4a – 4m was developed. These compounds serve as synthones for further
transformations towards potentially bioactive derivatives.
Experimental Part
General. Reagent-grade chemicals were purchased from commercial sources and further purified
before use. Column chromatography (CC): Merck silica gel 60 (SiO2; 230 – 400 mesh). M.p.: in open

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capillaries; uncorrected. Progress of the reaction was monitored by silica gel-G coated TLC plates with
MeOH/CHCl3 as the eluent; the spots were visualized by exposing the dry plate to I2 vapor. IR Spectra:
1
KBr disc; Shimadzu 8201 PC, FT-IR spectrophotometer; in cmꢀ1. H- and 13C-NMR spectra: Bruker
DRX-300 spectrometer in CDCl3, at 300 and 75 MHz, resp.; TMS as an internal standard; chemical shifts
in d [ppm]. FAB-MS: Jeol SX-102 mass spectrometer. Elemental analyses: Carlo Erba-1108 analyzer.
The anal. data of all the compounds were satisfactory.
Synthesis of 10-(3-Chloropropyl)-10H-phenothiazine (1). See [10].
Synthesis of 1-[3-(10H-Phenothiazin-10-yl)propyl]urea (2). See [11].
General Procedure for the Synthesis of 1-(Arylmethylidene)-3-[3-(10H-phenothiazin-10-yl)propyl]-
ureas 3. A soln. of 2 (0.026 mol) and aromatic aldehyde (0.026 mol) in EtOH (100 ml) in the presence of
2 – 4 drops of AcOH was first magnetically stirred for ca. 2.0 h at r.t., followed by heating to reflux on a
steam bath for ca. 3.3 h. The reaction was monitored by TLC. The product was filtered, cooled, and
purified by CC (CHCl3/MeOH 7:3; 90 ml). The purified product was dried under vacuum and
recrystallized from acetone to furnish compound 3.
1-[3-(10H-Phenothiazin-10-yl)propyl]-3-(phenylmethylidene)urea (3a). Yield: 6.29 g (64%). M.p.
153 – 1558. IR: 684 (CꢀSꢀC), 1332 (NꢀC), 1464 (C¼C), 1541 (N¼CH), 1664 (CO), 1430, 2836, 2894
(CH2), 3022 (arom. CH), 3363 (NH). 1H-NMR (300 MHz, CDCl3): 2.08 – 2.15 (m, CH2); 3.31 – 3.37 (m,
CH2NH); 4.19 (t, J ¼ 7.4, CH2N); 5.78 (s, NH); 7.96 (s, CH¼N); 6.05 – 8.10 (m, 13 arom. H). 13C-NMR
(75 MHz, CDCl3): 35.5 (CH2), 42.6 (CH2NH); 48.8 (CH2N); 109.1 (C(4), C(5)); 116.7 (C(1), C(8));
120.8 (C(2), C(7)); 121.6 (C(3), C(6)); 123.6 (2 Co)); 125.5 (2 Cm); 126.8 (Cp); 135.6 (Cipso); 136.9 (C(4a),
C(5a)); 144.7 (C(1a), C(8a)); 152.6 (CH¼N); 160.4 (C¼O). FAB-MS: 387 (Mþ). Anal. calc. for
C23H21N3OS (387.50): C 71.29, H 5.46, N 10.84; found: C 71.24, H 5.38, N 10.81.
1-[(4-Chlorophenyl)methylidene]-3-[3-(10H-phenothiazin-10-yl)propyl]urea (3b). Yield: 7.24 g
(66%). M.p. 161 – 1628. IR: 684 (CꢀSꢀC), 740 (CꢀCl), 1303 (NꢀC), 1472 (C¼C), 1548 (N¼CH), 1648
1
(CO), 1448, 2869, 2913 (CH2), 3031 (arom. CH), 3369 (NH). H-NMR (300 MHz, CDCl3): 2.18 – 2.22
(m, CH2); 3.42 – 3.46 (m, CH2NH); 4.29 (t, J ¼ 7.4, CH2N); 5.82 (s, NH); 7.98 (s, CH¼N); 6.80 – 7.79 (m,
12 arom. H). 13C-NMR (75 MHz, CDCl3): 38.6 (CH2); 44.4 (CH2NH); 51.8 (CH2N); 110.7 (C(4), C(5));
120.4 (C(1), C(8)); 124.5 (C(2), C(7)); 125.4 (C(3), C(6)); 127.6 (2 Co); 126.5 (2 Cm); 128.8, 137.3 (2 Cp);
138.4 (C(4a), C(5a)); 148.3 (C(1a), C(8a)); 153.2 (CH¼N); 165.8 (C¼O). FAB-MS: 421 (Mþ). Anal.
calc. for C23H20ClN3OS (421.95): C 65.47, H 4.77, N 9.95; found: C 65.43, H 4.65, N 9.91.
1-[(3-Chlorophenyl)methylidene]-3-[3-(10H-phenothiazin-10-yl)propyl]urea (3c). Yield: 7.0 g
(64%). M.p. 165 – 1668. IR: 693 (CꢀSꢀC), 744 (CꢀCl), 1344 (NꢀC), 1476 (C¼C), 1551 (N¼CH), 1676
1
(CO), 1440, 2845, 2902 (CH2), 3033 (arom. CH), 3372 (NH). H-NMR (300 MHz, CDCl3): 2.20 – 2.25
(m, CH2); 3.45 – 3.49 (m, CH2NH); 4.27 (t, J ¼ 7.4, CH2N); 5.88 (s, NH); 7.97 (s, CH¼N); 6.50 – 7.81 (m,
12 arom. H). 13C-NMR (75 MHz, CDCl3): 37.3 (CH2); 45.8 (CH2NH); 52.9 (CH2N); 111.6 (C(4), C(5));
120.3 (C(1), C(8)); 124.5 (C(2), C(7)); 125.6 (C(3), C(6)); 126.3, 126.8 (2 Co); 127.4, 127.9 (2 Cm); 128.5,
137.2 (2 Cp); 138.1 (C(4a), C(5a)); 146.5 (C(1a), C(8a)); 157.5 (CH¼N); 163.6 (C¼O). FAB-MS: 421
(Mþ). Anal. calc. for C23H20ClN3OS (421.95): C 65.47, H 4.77, N 9.95; found: C 65.42, H 4.68, N 9.93.
1-[(2-Chlorophenyl)methylidene]-3-[3-(10H-phenothiazin-10-yl)propyl]urea (3d). Yield: 7.46 g
(68%). M.p. 168 – 1698. IR: 692 (CꢀSꢀC), 753 (CꢀCl), 1338 (NꢀC), 1474 (C¼C), 1553 (N¼CH), 1674
1
(CO), 1439, 2848, 2906 (CH2), 3034 (arom. CH), 3373 (NH). H-NMR (300 MHz, CDCl3): 2.11 – 2.15
(m, CH2); 3.42 – 3.47 (m, CH2NH); 4.30 (t, J ¼ 7.4, CH2N); 5.82 (s, NH); 7.96 (s, CH¼N); 6.48 – 7.86 (m,
12 arom. H). 13C-NMR (75 MHz, CDCl3): 39.2 (CH2); 42.7 (CH2NH); 51.7 (CH2N); 111.3 (C(4), C(5));
119.4 (C(1), C(8)); 123.4 (C(2), C(7)); 124.1 (C(3), C(6)); 126.5, 127.4 (2 Co); 128.1, 128.8 (2 Cm); 129.5,
136.1 (2 Cp); 137.7 (C(4a), C(5a)); 149.9 (C(1a), C(8a)); 157.6 (CH¼N); 162.7 (C¼O). FAB-MS: 421
(Mþ). Anal. calc. for C23H20ClN3OS (421.95): C 65.47, H 4.77, N 9.95; found: C 65.45, H 4.69, N 9.90.
1-[(4-Bromophenyl)methylidene]-3-[3-(10H-phenothiazin-10-yl)propyl]urea (3e). Yield: 7.87 g
(65%). M.p. 165 – 1668. IR: 636 (CꢀBr), 697 (CꢀSꢀC), 1342 (NꢀC), 1472 (C¼C), 1549 (N¼CH),
1672 (CO), 1441, 2850, 2907 (CH2), 3037 (arom. CH), 3376 (NH). 1H-NMR (300 MHz, CDCl3): 2.18 –
2.22 (m, CH2); 3.41 – 3.46 (m, CH2NH); 4.31 (t, J ¼ 7.5, CH2N); 5.90 (s, NH); 8.02 (s, CH¼N); 6.42 – 7.76
(m, 12 arom. H). 13C-NMR (75 MHz, CDCl3): 38.3 (CH2); 45.1 (CH2NH); 51.3 (CH2N); 112.5 (C(4),
C(5)); 117.8 (C(1), C(8)); 122.7 (C(2), C(7)); 123.8 (C(3), C(6)); 124.4 (2 Co); 127.3 (2 Cm); 128.8, 140.8

Helvetica Chimica Acta – Vol. 95 (2012)
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(2 Cp); 141.2 (C(4a), C(5a)); 147.4 (C(1a), C(8a)); 154.7 (CH¼N); 162.3 (C¼O). FAB-MS: 466 (Mþ).
Anal. calc. for C23H20BrN3OS (466.40): C 59.23, H 4.32, N 9.00; found: C 59.15, H 4.23, N 8.94.
1-[(3-Bromophenyl)methylidene]-3-[3-(10H-phenothiazin-10-yl)propyl]urea (3f). Yield: 7.51 g
(62%). M.p. 163 – 1648. IR: 643 (CꢀBr), 691 (CꢀSꢀC), 1346 (NꢀC), 1479 (C¼C), 1552 (N¼CH),
1677 (CO), 1445, 2852, 2910 (CH2), 3035 (arom. CH), 3378 (NH). 1H-NMR (300 MHz, CDCl3): 2.20 –
2.25 (m, CH2); 3.36 – 3.43 (m, CH2NH); 4.37 (t, J ¼ 7.6, CH2N); 5.86 (s, NH); 7.95 (s, CH¼N); 6.37 – 7.81
(m, 12 arom. H). 13C-NMR (75 MHz, CDCl3): 37.5 (CH2); 44.2 (CH2NH); 49.4 (CH2N); 112.2 (C(4),
C(5)); 117.5 (C(1), C(8)); 122.6 (C(2), C(7)); 123.4 (C(3), C(6)); 125.3, 126.4 (2 Co); 128.5, 128.9 (2 Cm);
129.6, 140.5 (2 Cp); 141.8 (C(4a), C(5a)); 145.3 (C(1a), C(8a)); 156.9 (CH¼N); 164.2 (C¼O). FAB-MS:
466 (Mþ). Anal. calc. for C23H20BrN3OS (466.40): C 59.23, H 4.32, N 9.00; found: C 59.18, H 4.28, N 8.97.
1-[(2-Bromophenyl)methylidene]-3-[3-(10H-phenothiazin-10-yl)propyl]urea (3g). Yield: 8.0 g
(66%). M.p. 164 – 1668. IR: 638 (CꢀBr), 699 (CꢀSꢀC), 1339 (NꢀC), 1473 (C¼C), 1554 (N¼CH),
1675 (CO), 1438, 2846, 2904 (CH2), 3040 (arom. CH), 3381 (NH). 1H-NMR (300 MHz, CDCl3): 2.27 –
2.32 (m, CH2); 3.43 – 3.48 (m, CH2NH); 4.29 (t, J ¼ 7.6, CH2N); 5.91 (s, NH); 7.98 (s, CH¼N); 6.43 – 7.89
(m, 12 arom. H). 13C-NMR (75 MHz, CDCl3): 38.8 (CH2); 46.3 (CH2NH); 50.5 (CH2N); 112.6 (C(4),
C(5)); 119.2 (C(1), C(8)); 123.5 (C(2), C(7)); 124.3 (C(3), C(6)); 125.9, 127.4 (2 Co); 127.6, 128.1 (2 Cm);
128.4, 139.0 (2 Cp); 140.6 (C(4a), C(5a)); 148.6 (C(1a), C(8a)); 155.8 (CH¼N); 161.6 (C¼O). FAB-MS:
466 (Mþ). Anal. calc. for C23H20BrN3OS (466.40): C 59.23, H 4.32, N 9.00; found: C 59.19, H 4.29, N 8.96.
1-[(4-Nitrophenyl)methylidene]-3-[3-(10H-phenothiazin-10-yl)propyl]urea (3h). Yield: 7.19 g
(64%). M.p. 160 – 1628. IR: 696 (CꢀSꢀC), 1337 (CꢀN), 1478 (C¼C), 1530 (N¼O), 1556 (N¼CH),
1680 (CO), 1444, 2851, 2909 (CH2), 3036 (arom. CH), 3374 (NH). 1H-NMR (300 MHz, CDCl3): 2.25 –
2.28 (m, CH2); 3.47 – 3.51 (m, CH2NH); 4.32 (t, J ¼ 7.6, CH2N); 5.87 (s, NH); 7.93 (s, CH¼N); 6.55 – 7.82
(m, 12 arom. H). 13C-NMR (75 MHz, CDCl3): 39.6 (CH2); 47.7 (CH2NH); 52.0 (CH2N); 113.7 (C(4),
C(5)); 118.3 (C(1), C(8)); 124.0 (C(2), C(7)); 125.3 (C(3), C(6)); 126.6 (2 Co); 128.7 (2 Cm); 129.3, 139.9
(2 Cp); 140.5 (C(4a), C(5a)); 149.2 (C(1a), C(8a)); 155.3 (CH¼N); 165.4 (C¼O). FAB-MS: 432 (Mþ).
Anal. calc. for C23H20N4O3S (432.50): C 63.87, H 4.66, N 12.95; found: C 63.74, H 4.61, N 12.91.
1-[(3-Nitrophenyl)methylidene]-3-[3-(10H-phenothiazin-10-yl)propyl]urea (3i). Yield: 7.53 g
(67%). M.p. 161 – 1638. IR: 694 (CꢀSꢀC), 1334 (CꢀN), 1475 (C¼C), 1528 (N¼O), 1551 (N¼CH),
1678 (CO), 1437, 2854, 2905 (CH2), 3031 (arom. CH), 3370 (NH). 1H-NMR (300 MHz, CDCl3): 2.14 –
2.19 (m, CH2); 3.40 – 3.44 (m, CH2NH); 4.25 (t, J ¼ 7.6, CH2N); 5.83 (s, NH); 8.05 (s, CH¼N); 6.46 – 7.91
(m, 12 arom. H). 13C-NMR (75 MHz, CDCl3): 36.9 (CH2); 47.4 (CH2NH); 52.6 (CH2N); 113.1 (C(4),
C(5)); 119.6 (C(1), C(8)); 125.7 (C(2), C(7)); 126.1 (C(3), C(6)); 127.2, 128.4 (2 Co); 129.0, 129.4 (2 Cm);
130.7, 138.4 (2 Cp); 139.2 (C(4a), C(5a)); 149.6 (C(1a), C(8a)); 154.5 (CH¼N); 164.4 (C¼O). FAB-MS:
432 (Mþ). Anal. calc. for C23H29N4O3S (432.50): C 63.87, H 4.66, N 12.95; found: C 63.78, H 4.63, N 12.92.
1-[(2-Nitrophenyl)methylidene]-3-[3-(10H-phenothiazin-10-yl)propyl]urea (3j). Yield: 7.30 g
(65%). M.p. 159 – 1608. IR: 698 (CꢀSꢀC), 1341 (CꢀNH), 1473 (C¼C), 1533 (N¼O), 1560 (N¼CH),
1671 (CO), 1446, 2849, 2912 (CH2), 3039 (arom. CH), 3379 (NH). 1H-NMR (300 MHz, CDCl3): 2.20 –
2.24 (m, CH2); 3.50 – 3.55 (m, CH2NH); 4.28 (t, J ¼ 7.6, CH2N); 5.92 (s, NH); 8.00 (s, CH¼N); 6.51 – 7.89
(m, 12 arom. H). 13C-NMR (75 MHz, CDCl3): 38.3 (CH2); 46.9 (CH2NH); 50.7 (CH2N); 111.8 (C(4),
C(5)); 118.2 (C(1), C(8)); 125.5 (C(2), C(7)); 126.4 (C(3), C(6)); 127.5, 128.2 (2 Co); 129.6, 130.1 (2 Cm);
130.4, 138.7 (2 Cp); 139.3 (C(4a), C(5a)); 147.0 (C(1a), C(8a)); 156.6 (CH¼N); 163.7 (C¼O). FAB-MS:
432 (Mþ). Anal. calc. for C23H29N4O3S (432.50): C 63.87, H 4.66, N 12.95; found: C 63.77, H 4.60, N 12.90.
1-[(4-Methoxyphenyl)methylidene]-3-[3-(10H-phenothiazin-10-yl)propyl]urea (3k). Yield: 6.73 g
(62%). M.p. 152 – 1548. IR: 702 (CꢀSꢀC), 1336 (NꢀC), 1467 (C¼C), 1543 (N¼CH), 1667 (CO), 1433,
2839, 2895 (CH2), 2947 (MeꢀO), 3024 (arom. CH), 3365 (NH). 1H-NMR (300 MHz, CDCl3): 2.11 – 2.16
(m, CH2); 3.33 – 3.38 (m, CH2NH); 3.51 (s, MeO); 4.22 (t, J ¼ 7.6, CH2N); 5.80 (s, NH); 7.89 (s, CH¼N);
6.27 – 7.62 (m, 12 arom. H). 13C-NMR (75 MHz, CDCl3): 36.2 (CH2); 43.5 (CH2NH); 44.4 (CH2N); 63.7
(MeO); 109.8 (C(4), C(5)); 116.0 (C(1), C(8)); 121.7 (C(2), C(7)); 122.4 (C(3), C(6)); 124.8 (2 Co);
126.0 (2 Cm); 127.7, 136.6 (2 Cp); 137.0 (C(4a), C(5a)); 144.6 (C(1a), C(8a)); 152.8 (CH¼N); 160.2
(C¼O). FAB-MS: 417 (Mþ). Anal. calc. for C24H23N3O2S (417.53): C 69.04, H 5.55, N 10.06; found: C
68.92, H 5.48, N 10.02.
1-[(4-Methylphenyl)methylidene]-3-[3-(10H-phenothiazin-10-yl)propyl]urea (3l). Yield: 6.0 g
(58%). M.p. 144 – 1468. IR: 699 (CꢀSꢀC), 1326 (NꢀC), 1460 (C¼C), 1539 (N¼CH), 1661 (CO), 1428,

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2833, 2891 (CH2), 2917 (Me); 3019 (arom. CH), 3360 (NH). 1H-NMR (300 MHz, CDCl3): 2.03 – 2.09 (m,
CH2); 2.39 (s, Me); 3.32 – 3.39 (m, CH2NH); 4.17 (t, J ¼ 7.4, CH2N); 5.74 (s, NH); 7.85 (s, CH¼N); 6.19 –
7.57 (m, 12 arom. H). 13C-NMR (75 MHz, CDCl3): 24.9 (Me); 35.3 (CH2); 42.5 (CH2NH); 48.4 (CH2N);
109.0 (C(4), C(5)); 115.3 (C(1), C(8)); 120.4 (C(2), C(7)); 121.2 (C(3), C(6)); 123.4 (2 Co); 125.2 (2 Cm);
126.3, 135.4 (2 Cp); 136.3 (C(4a), C(5a)); 144.5 (C(1a), C(8a)); 152.1 (CH¼N); 160.0 (C¼O). FAB-MS:
401 (Mþ). Anal. calc. for C24H23N3OS (401.53): C 71.79, H 5.77, N 10.46; found: C 71.75, H 5.73, N 10.44.
1-[(4-Hydroxyphenyl)methylidene]-3-[3-(10H-phenothiazin-10-yl)propyl]urea (3m). Yield: 6.81 g
(65%). M.p. 162 – 1648. IR: 702 (CꢀSꢀC), 1337 (NꢀC), 1468 (C¼C), 1546 (N¼CH), 1670 (CO), 1435,
1
2841, 2898 (CH2), 3027 (arom. CH), 3368 (NH), 3472 (OH). H-NMR (300 MHz, CDCl3): 2.11 – 2.16
(m, CH2); 3.40 – 3.47 (m, CH2NH); 4.09 (s, OH); 4.23 (t, J ¼ 7.65, CH2N); 5.81 (s, NH); 7.92 (s, CH¼N);
6.32 – 7.71 (m, 12 arom. H). 13C-NMR (75 MHz, CDCl3): 36.7 (CH2); 43.2 (CH2NH); 49.5 (CH2N); 110.2
(C(4), C(5)); 116.4 (C(1), C(8)); 121.6 (C(2), C(7)); 122.2 (C(3), C(6)); 124.6 (2 Co); 126.1 (2 Cm); 127.4,
136.5 (2 Cp); 137.2 (C(4a), C(5a)); 144.7 (C(1a), C(8a)); 153.1 (CH¼N); 161.5 (C¼O). FAB-MS: 403
(Mþ). Anal. calc. for C23H21N3O2S (403.50): C 68.46, H 5.24, N 10.41; found: C 68.41, H 5.22, N 10.35.
General Procedure for the Synthesis of 4-Aryl-3-chloro-2-oxo-N-[3-(10H-phenothiazin-10-yl)pro-
pyl]azetidine-1-carboxamides 4. A soln. of 3 (0.007 mol), ClCH2COCl (0.007 mol), and Et3N (0.007 mol)
in MeOH (50 ml) was first magnetically stirred for ca. 2.0 h at r.t., followed by heating to reflux on a
steam bath for ca. 4.0 h. The completion of the reaction was monitored by TLC. The product was filtered
and purified by CC using MeOH/CHCl3 (7:3 v/v) as eluent (70 ml). The purified product was dried
under vacuum and recrystallized from EtOH to furnish compound 4.
trans-3-Chloro-2-oxo-N-[3-(10H-phenothiazin-10-yl)propyl]-4-phenylazetidine-1-carboxamide
(trans-4a). Yield: 1.94 g (60%). M.p. 148 – 1498. IR: 692 (CꢀSꢀC), 1331 (CꢀN), 1472 (C¼C), 1664 (CO),
1730 (C(2)¼O), 1434, 2841, 2900 (CH2), 2906 (CH(3)), 3025 (arom. CH), 3369 (NH). 1H-NMR
(300 MHz, CDCl3): 2.10 – 2.14 (m, CH2); 3.30 – 3.34 (m, CH2NH); 4.05 (t, J ¼ 7.4, CH2N); 4.44 (d, J ¼
5.00, CH(3)); 5.12 (d, J ¼ 5.00, CH(4)); 5.72 (s, NH); 6.40 – 7.74 (m, 13 arom. H). 13C-NMR
(75 MHz, CDCl3): 37.8 (CH2); 43.9 (CH2NH); 50.7 (CH2N); 52.1 (CH(3)); 60.7 (CH(4)); 110.6 (C(4’’),
C(5’’)); 116.9 (C(1’’), C(8’’)); 121.4 (C(2’’), C(7’’)); 122.7 (C(3’’), C(6)); 124.4 (2 Co); 126.6 (2 Cm); 127.6
(Cp); 136.7 (Cipso); 137.7 (C(4a’’), C(5a’’)); 145.3 (C(1a’’), C(8a’’)); 161.6 (C¼O); 165.7 (C¼O). FAB-MS:
464 (Mþ). Anal. calc. for C25H22ClN3O2S (463.99): C 64.71, H 4.77, N 9.05; found: C 64.62, H 4.72, N 9.01.
trans-3-Chloro-2-(4-chlorophenyl)-4-oxo-N-[3-(10H-phenothiazin-10-yl)propyl]azetidine-1-carbox-
amide (trans-4b). Yield: 2.16 g (62%). M.p. 160 – 1618. IR: 695 (CꢀSꢀC), 765 (CꢀCl), 1342 (CꢀN), 1479
(C¼C), 1558 (N¼N), 1670 (CO), 1737 (C(4)¼O), 1439, 2846, 2905 (CH2), 2911 (CH(3)), 3032 (arom.
1
CH), 3376 (NH). H-NMR (300 MHz, CDCl3): 2.20 – 2.26 (m, CH2); 3.35 – 3.41 (m, CH2NH); 4.16 (t,
J ¼ 7.6, CH2N); 4.53 (d, J ¼ 5.1, CH(3)); 5.25 (d, J ¼ 5.1, CH(2)); 5.81 (s, NH); 6.82 – 7.99 (m, 12 arom.
H). 13C-NMR (75 MHz, CDCl3): 40.4 (CH2); 47.7 (CH2NH); 52.6 (CH2N); 54.4 (CH(3)); 61.9 (CH(2));
114.5 (C(4’’), C(5)); 121.4 (C(1’’), C(8’’)); 125.2 (C(2’’), C(7’’)); 126.9 (C(3’’), C(6’’)); 128.9 (2 Co); 130.3
(2 Cm); 131.1, 139.8 (2 Cp); 140.6 (C(4a’’), C(5a’’)); 146.4 (C(1a’’), C(8a’’)); 162.7 (C¼O); 166.7 (C¼O).
FAB-MS: 498 (Mþ). Anal. calc. for C25H21Cl2N3O2S (498.43): C 60.24, H 4.24, N 8.43; found: C 60.16, H
4.19, N 8.36.
trans-3-Chloro-2-(3-chlorophenyl)-4-oxo-N-[3-(10H-phenothiazin-10-yl)propyl]azetidine-1-carbox-
amide (trans-4c). Yield: 2.26 g (65%). M.p. 158 – 1598. IR: 701 (CꢀSꢀC), 776 (CꢀCl), 1345 (CꢀN), 1483
(C¼C), 1561 (N¼N), 1673 (CO), 1740 (C(4)¼O), 1443, 2851, 2910 (CH2), 2916 (CH(3)), 3036 (arom.
1
CH), 3380 (NH). H-NMR (300 MHz, CDCl3): 2.21 – 2.27 (m, CH2); 3.37 – 3.41 (m, CH2NH); 4.18 (t,
J ¼ 7.5, CH2N); 4.55 (d, J ¼ 5.1, CH(3)); 5.21 (d, J ¼ 5.1, CH(2)); 5.87 (s, NH); 6.77 – 7.90 (m, 12 arom.
H). 13C-NMR (75 MHz, CDCl3): 40.7 (CH2); 48.5 (CH2NH); 52.5 (CH2N); 55.8 (CH(3)); 63.2 (CH(2));
115.5 (C(4’’), C(5’’)); 121.7 (C(1’’), C(8’’)); 125.4 (C(2’’), C(7’’)); 127.7 (C(3’’), C(6’’)); 128.4, 129.2 (2 Co);
130.2, 130.7 (2 Cm); 131.4, 141.5 (2 Cp); 142.4 (C(4a’’), C(5a’’)); 149.5 (C(1a’’), C(8a’’)); 163.5 (C¼O);
167.9 (C¼O). FAB-MS: 498 (Mþ). Anal. calc. for C25H21Cl2N3O2S (498.43): C 60.24, H 4.24, N 8.43;
found: C 60.18, H 4.22, N 8.38.
trans-3-Chloro-2-(2-chlorophenyl)-4-oxo-N-[3-(10H-phenothiazin-10-yl)propyl]azetidine-1-carbox-
amide (trans-4d). Yield: 2.09 g (60%). M.p. 160 – 1628. IR: 706 (CꢀSꢀC), 773 (CꢀCl), 1338 (CꢀN), 1482
(C¼C), 1562 (N¼N), 1669 (CO), 1741 (C(4)¼O), 1440, 2853, 2906 (CH2), 2912 (CHꢀCl), 3031 (arom.
1
CH), 3382 (NH). H-NMR (300 MHz, CDCl3): 2.30 – 2.35 (m, CH2); 3.41 – 3.45 (m, CH2NH); 4.21 (t,

Helvetica Chimica Acta – Vol. 95 (2012)
519
J ¼ 7.6, CH2N); 4.59 (d, J ¼ 5.1, CH(3)); 5.30 (d, J ¼ 5.1, CH(2)); 5.84 (s, NH); 6.79 – 7.85 (m, 12 arom.
H). 13C-NMR (75 MHz, CDCl3): 38.8 (CH2); 47.6 (CH2NH); 51.2 (CH2N); 56.3 (CH(3)); 63.6 (CH(2));
113.1 (C(4’’), C(5’’)); 118.9 (C(1’’), C(8’’)); 123.1 (C(2’’), C(7’’)); 124.6 (C(3’’), C(6’’)); 126.5, 127.2 (2 Co);
128.1, 128.8 (2 Cm); 129.8, 141.6 (2 Cp); 142.5 (C(4a’’), C(5a’’)); 148.3 (C(1a’’), C(8a’’)); 165.4 (C¼O);
168.6 (C¼O). FAB-MS: 498 (Mþ). Anal. calc. for C25H21Cl2N3O2S (498.43): C 60.24, H 4.24, N 8.43;
found: C 60.15, H 4.18, N 8.40.
trans-2-(4-Bromophenyl)-3-chloro-4-oxo-N-[3-(10H-phenothiazin-10-yl)propyl]azetidine-1-carbox-
amide (trans-4e). Yield: 2.35 g (62%). M.p. 156 – 1588. IR: 578 (CꢀBr), 710 (CꢀSꢀC), 1343 (CꢀN), 1480
(C¼C), 1559 (N¼N), 1679 (CO), 1742 (C(4)¼O), 1444, 2847, 2904 (CH2), 2945 (CH(3)), 3033 (arom.
1
CH), 3377 (NH). H-NMR (300 MHz, CDCl3): 2.07 – 2.11 (m, CH2); 3.40 – 3.44 (m, CH2NH); 4.23 (t,
J ¼ 7.6, CH2N); 4.59 (d, J ¼ 5.2, CH(3)); 5.21 (d, J ¼ 5.2, CH(2)); 5.86 (s, NH); 6.80 – 8.05 (m, 12 arom.
H). 13C-NMR (75 MHz, CDCl3): 41.3 (CH2); 46.4 (CH2NH); 53.1 (CH2N); 53.7 (CH(3)); 62.3 (CH(2));
115.8 (C(4’’), C(5’’)); 118.5 (C(1’’), C(8’’)); 124.2 (C(2’’), C(7’’)); 125.4 (C(3’’), C(6’’)); 127.6 (2 Co); 129.6
(2 Cm); 130.1, 139.5 (2 Cp); 140.7 (C(4a’’), C(5a’’)); 147.0 (C(1a’’), C(8a’’)); 165.8 (C¼O); 169.5 (C¼O).
FAB-MS: 543 (Mþ). Anal. calc. for C25H21BrClN3O2S (542.88): C 55.31, H 3.89, N 7.74; found: C 55.26, H
3.83, N 7.68.
trans-2-(3-Bromophenyl)-3-chloro-4-oxo-N-[3-(10H-phenothiazin-10-yl)propyl]azetidine-1-carbox-
amide (trans-4f). Yield: 2.43 g (64%). M.p. 157 – 1598. IR: 572 (CꢀBr), 705 (CꢀSꢀC), 1347 (CꢀNH),
1484 (C¼C), 1564 (N¼N), 1677 (CO), 1735 (C(4)¼O), 1448, 2850, 2909 (CH2), 2938 (CH(3)), 3037
1
(arom. CH), 3384 (NH). H-NMR (300 MHz, CDCl3): 2.20 – 2.27 (m, CH2); 3.41 – 3.48 (m, CH2NH);
4.22 (t, J ¼ 7.7, CH2N); 4.54 (d, J ¼ 5.2, CH(3)); 5.27 (d, J ¼ 5.2, CH(2)); 5.83 (s, NH); 6.41 – 7.83 (m, 12
arom. H). 13C-NMR (75 MHz, CDCl3): 39.2 (CH2); 44.5 (CH2NH); 51.7 (CH2N); 55.6 (CH(3)); 65.7
(CH(2)); 111.4 (C(4’’), C(5’’)); 117.6 (C(1’’), C(8’’)); 124.7 (C(2’’), C(7’’)); 125.8 (C(3’’), C(6)); 127.9,
128.1 (2 Co); 129.5, 129.8 (2 Cm); 130.5, 137.7 (2 Cp); 138.6 (C(4a’’), C(5a’’)); 148.1 (C(1a’’), C(8a’’)); 164.4
(C¼O); 169.1 (C¼O). FAB-MS: 543 (Mþ). Anal. calc. for C25H21BrClN3O2S (542.88): C 55.31, H 3.89, N
7.74; found: C 55.22, H 3.87, N 7.65.
trans-2-(2-Bromophenyl)-3-chloro-4-oxo-N-[3-(10H-phenothiazin-10-yl)propyl]azetidine-1-carbox-
amide (trans-4g). Yield: 2.39 g (63%). M.p. 154 – 1568. IR: 543 (CꢀBr), 700 (CꢀSꢀC), 1353 (CꢀNH),
1460 (C¼C), 1568 (N¼N), 1673 (CO), 1746 (C(4)¼O), 1440, 2850, 2911 (CH2), 2952 (CH(3)), 3016
1
(arom. CH), 3341 (NH). H-NMR (300 MHz, CDCl3): 2.22 – 2.29 (m, CH2); 3.45 – 3.51 (m, CH2NH);
4.14 (t, J ¼ 7.6, CH2N); 4.56 (d, J ¼ 5.2, CH(3)); 5.30 (d, J ¼ 5.2, CH(2)); 5.92 (s, NH); 6.37 – 7.82 (m, 12
arom. H). 13C-NMR (75 MHz, CDCl3): 39.1 (CH2); 48.6 (CH2NH); 53.5 (CH2N); 56.7 (CH(3)); 65.3
(CH(2)); 112.6 (C(4’’), C(5’’)); 119.3 (C(1’’), C(8’’)); 125.0 (C(2’’), C(7’’)); 126.7 (C(3’’), C(6’’)); 128.3,
129.4 (2 Co); 130.3, 130.8 (2 Cm); 131.7, 138.7 (2 Cp); 139.6 (C(4a’’), C(5a’’)); 146.3 (C(1a’’), C(8a’’)); 164.7
(C¼O); 170.7 (C¼O). FAB-MS: 543 (Mþ). Anal. calc. for C25H21BrClN3O2S (542.88): C 55.31, H 3.89, N
7.74; found: C 55.24, H 3.85, N 7.69.
trans-3-Chloro-2-(4-nitrophenyl)-4-oxo-N-[3-(10H-phenothiazin-10-yl)propyl]azetidine-1-carbox-
amide (trans-4h). Yield: 2.13 g (60%). M.p. 152 – 1538. IR: 696 (CꢀSꢀC), 868 (CꢀNO), 1357 (CꢀN),
1487 (C¼C), 1540 (NO2), 1570 (N¼N), 1675 (CO), 1738 (C(4)¼O), 1449, 2854, 2905 (CH2), 2921
1
(CHꢀCl), 3038 (arom. CH), 3382 (NH). H-NMR (300 MHz, CDCl3): 2.20 – 2.25 (m, CH2); 3.31 – 3.37
(m, CH2NH); 4.24 (t, J ¼ 7.7, CH2N); 5.31 (d, J ¼ 5.3, CH(2)); 4.61 (d, J ¼ 5.3, CH(3)); 5.82 (s, NH);
6.49 – 7.76 (m, 12 arom. H). 13C-NMR (75 MHz, CDCl3): 41.8 (CH2); 46.7 (CH2NH); 55.5 (CH2N); 55.9
(CH(3)); 64.4 (CH(2)); 113.7 (C(4’’), C(5’’)); 119.4 (C(1’’), C(8’’)); 123.4 (C(2’’), C(7’’)); 124.9 (C(3),
C(6)); 126.5 (2 Co); 128.7 (2 Cm); 129.6, 140.8 (2 Cp); 141.1 (C(4a’’), C(5a’’)); 149.7 (C(1a’’), C(8a’’));
163.4 (C¼O); 167.8 (C¼O). FAB-MS: 509 (Mþ). Anal. calc. for C25H21ClN4O4S (508.98): C 58.99, H 4.15,
N 11.00; found: C 58.91, H 4.08, N 10.92.
trans-3-Chloro-2-(3-nitrophenyl)-4-oxo-N-[3-(10H-phenothiazin-10-yl)propyl]azetidine-1-carbox-
amide (trans-4i). Yield: 2.28 g (64%). M.p. 155 – 1578. IR: 694 (CꢀSꢀC), 864 (CꢀNO), 1358 (CꢀN), 1481
(C¼C), 1542 (NO2), 1566 (N¼N), 1672 (CO), 1743 (C(4)¼O), 1452, 2858, 2912 (CH2), 2919 (CH(3)),
3042 (arom. CH), 3378 (NH). 1H-NMR (300 MHz, CDCl3): 2.23 – 2.29 (m, CH2); 3.36 – 3.42 (m,
CH2NH); 4.12 (t, J ¼ 7.6, CH2N); 4.57 (d, J ¼ 5.2, CH(3)); 5.19 (d, J ¼ 5.2, CH(2)); 5.89 (s, NH); 6.36 –
7.71 (m, 12 arom. H). 13C-NMR (75 MHz, CDCl3): 41.9 (CH2); 47.4 (CH2NH); 53.3 (CH2N); 56.5
(CH(3)); 64.8 (C(2)); 114.4 (C(4’’), C(5’’)); 120.0 (C(1’’), C(8’’)); 122.5 (C(2’’), C(7’’)); 123.4 (C(3’’),

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Helvetica Chimica Acta – Vol. 95 (2012)
C(6’’)); 125.1, 126.2 (2 Co); 127.3, 127.9 (2 Cm); 128.4, 140.5 (2 Cp); 141.7 (C(4a’’), C(5a’’)); 147.8 (C(1a’’),
C(8a’’)); 163.6 (C¼O); 168.5 (C¼O). FAB-MS: 509 (Mþ). Anal. calc. for C25H21ClN4O4S (508.98): C
58.99, H 4.15, N 11.00; found: C 58.94, H 4.10, N 10.95.
trans-3-Chloro-2-(2-nitrophenyl)-4-oxo-N-[3-(10H-phenothiazin-10-yl)propyl]azetidine-1-carbox-
amide (trans-4j). Yield: 2.17 g (61%). M.p. 159 – 1608. IR: 690 (CꢀSꢀC), 869 (CꢀNO), 1355 (CꢀN), 1485
(C¼C), 1542 (NO2), 1569 (N¼N), 1680 (CO), 1745 (C(4)¼O), 1447, 2849, 2907 (CH2), 2924 (CHꢀCl),
3035 (arom. CH), 3381 (NH). 1H-NMR (300 MHz, CDCl3): 2.26 – 2.32 (m, CH2); 3.42 – 3.47 (m,
CH2NH); 4.13 (t, J ¼ 7.5, CH2N); 4.58 (d, J ¼ 5.3, CH(3)); 5.23 (d, J ¼ 5.3, CH(2)); 5.85 (s, NH); 6.42 –
7.80 (m, 12 arom. H). 13C-NMR (75 MHz, CDCl3): 40.4 (CH2); 45.8 (CH2NH); 54.1 (CH2N); 54.7
(CH(3)); 62.3 (C(2)); 113.3 (C(4’’), C(5’’)); 120.6 (C(1’’), C(8’’)); 123.1 (C(2’’), C(7’’)); 124.2 (C(3’’),
C(6’’)); 126.0, 127.4 (2 Co); 128.7, 129.1 (2 Cm); 129.6, 138.5 (2 Cp); 139.3 (C(4a’’), C(5a’’)); 147.6 (C(1a’’),
C(8a’’)); 162.5 (C¼O); 170.7 (C¼O). FAB-MS: 509 (Mþ). Anal. calc. for C25H21ClN4O4S (508.98): C
58.99, H 4.15, N 11.00; found: C 58.89, H 4.12, N 10.96.
trans-3-Chloro-2-(4-methoxyphenyl)-4-oxo-N-[3-(10H-phenothiazin-10-yl)propyl]azetidine-1-carb-
oxamide (trans-4k). Yield: 2.17 g (63%). M.p. 156 – 1578. IR: 696 (CꢀSꢀC), 1165 (CꢀO); 1329 (NꢀC),
1475 (C¼C), 1555 (N¼N), 1666 (CO), 1731 (C(4)¼O), 1437, 2843, 2901 (CH2), 2909 (CH(3)), 3028
1
(arom. CH), 3372 (NH). H-NMR (300 MHz, CDCl3): 2.14 – 2.19 (m, CH2); 3.31 – 3.35 (m, CH2NH);
3.71 (s, MeO); 4.07 (t, J ¼ 7.6, CH2N); 4.48 (d, J ¼ 5.1, CH(3)); 5.16 (d, J ¼ 5.1, CH(2)); 5.77 (s, NH);
6.37 – 7.75 (m, 12 arom. H). 13C-NMR (75 MHz, CDCl3): 38.2 (CH2); 44.1 (CH2NH); 50.9 (CH2N); 52.6
(CH(3)); 61.1 (C(2)); 110.8 (C(4’’), C(5’’)); 116.7 (C(1’’), C(8’’)); 121.9 (C(2’’), C(7’’)); 123.0 (C(3’’),
C(6’’)); 124.6 (2 Co); 126.9 (2 Cm); 128.1, 136.8 (2 Cp); 138.2 (C(4a’’), C(5a’’)); 145.5 (C(1a’’), C(8a’’));
161.9 (C¼O); 166.0 (C¼O). FAB-MS: 494 (Mþ). Anal. calc. for C26H24ClN3O3S (494.01): C 63.21, H 4.89,
N 8.50; found: C 63.15, H 4.84, N 8.46.
trans-3-Chloro-2-(4-methylphenyl)-4-oxo-N-[3-(10H-phenothiazin-10-yl)propyl]azetidine-1-carbox-
amide (trans-4l). Yield: 1.84 g (55%). M.p. 149 – 1518. IR: 697 (CꢀSꢀC), 1327 (CꢀN), 1469 (C¼C), 1551
(N¼N), 1663 (CO), 1725 (C(4)¼O), 1432, 2836, 2898 (CH2), 2905 (CH(3)), 3024 (arom. CH), 3367
(NH); 2927 (Me). 1H-NMR (300 MHz, CDCl3): 2.10 – 2.15 (m, CH2); 2.64 (s, Me); 3.25 – 3.32 (m,
CH2NH); 4.03 (t, J ¼ 7.5, CH2N); 4.40 (d, J ¼ 5.0, CH(3)); 5.09 (d, J ¼ 5.0, CH(2)); 5.68 (s, NH); 6.48 –
7.93 (m, 12 arom. H). 13C-NMR (75 MHz, CDCl3): 24.7 (Me); 37.5 (CH2); 43.2 (CH2NH); 50.1 (CH2N);
51.6 (CH(3)); 60.2 (C(2)); 110.2 (C(4’’), C(5’’)); 116.7 (C(1’’), C(8’’)); 121.1 (C(2’’), C(7’’)); 122.3 (C(3’’),
C(6’’)); 124.6 (2 Co); 126.1 (2 Cm); 127.2, 136.1 (2 Cp); 137.2 (C(4a’’), C(5a’’)); 145.1 (C(1a’’), C(8a’’));
161.3 (C¼O); 165.6 (C¼O). FAB-MS: 478 (Mþ). Anal. calc. for C26H24ClN3O2S (478.01): C 65.32, H 5.06,
N 8.79; found: C 65.29, H 5.05, N 8.78.
trans-3-Chloro-2-(4-hydroxyphenyl)-4-oxo-N-[3-(10H-phenothiazin-10-yl)propyl]azetidine-1-carb-
oxamide (trans-4m). Yield: 2.21 g (66%). M.p. 154 – 1558. IR: 699 (CꢀSꢀC), 1336 (CꢀNH), 1478 (C¼C),
1556 (N¼N), 1669 (CO), 1734 (C(4)¼O), 1438, 2845, 2903 (CH2), 2910 (CH(3)), 3030 (arom. CH), 3375
(NH); 3467 (OH). 1H-NMR (300 MHz, CDCl3): 2.19 – 2.25 (m, CH2); 3.33 – 3.39 (m, CH2NH); 4.09 (t,
J ¼ 7.7, CH2N); 4.17 (s, OH); 4.50 (d, J ¼ 5.2, CH(3)); 5.17 (d, J ¼ 5.2, CH(2)); 5.79 (s, NH); 6.33 – 7.81
(m, 12 arom. H). 13C-NMR (75 MHz, CDCl3): 38.3 (CH2); 44.7 (CH2NH); 50.9 (CH2N); 52.7 (CH(3));
61.6 (C(2)); 111.3 (C(4’’), C(5’’)); 117.2 (C(1’’), C(8’’)); 122.6 (C(2’’), C(7’’)); 123.8 (C(3’’), C(6’’)); 125.5
(2 Co); 127.7 (2 Cm); 128.4 , 137.0 (2 Cp); 138.8 (C(4a’’), C(5a’’)); 145.6 (C(1a’’), C(8a’’)); 161.9 (C¼O);
166.0 (C¼O). FAB-MS: 480 (Mþ). Anal. calc. for C25H22ClN3O3S (479.99): C 62.52, H 4.61, N 8.75;
found: C 62.47, H 4.57, N 8.71.
The authors are grateful to SAIF, Central Drugs Research Institute, Lucknow, India, for providing
spectral and analytical data of the compounds. We are also thankful to the head of the Department of
Chemistry, Dr. H. S. Gour, University, Sagar, India, for enabling us to carry out this work.
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Received September 14, 2011