Synthesis of some new mono- and bis-polycyclic aromatic spiro and bis-nonspiro-β-lactams

Article abstract of DOI:10.3390/molecules15010515

Some new mono-and bis-polycyclic aromatic spiro-β-lactams and bis-non spiropolycyclic aromatic β-lactams have been synthesized from imines derived from anthracene-9-carbaldehyde, 2-naphtaldehyde and a ketene derived from 9H-xanthene-9carboxylic acid and p

Full text of DOI:10.3390/molecules15010515

Molecules 2010, 15, 515-531; doi:10.3390/molecules15010515
OPEN ACCESS
molecules
ISSN 1420-3049
www.mdpi.com/journal/molecules
Article
Synthesis of Some New Mono- and Bis-Polycyclic Aromatic
Spiro and Bis-Nonspiro-β-Lactams
Aliasghar Jarrahpour * and Edris Ebrahimi
Department of Chemistry, College of Sciences, Shiraz University, Shiraz, 71454, Iran;
E-Mail: edris.ebrahimi@gmail.com (E.E.)
* Author to whom correspondence should be addressed; E-Mail: aliasghar6683@yahoo.com or
jarrah@susc.ac.ir; Tel.: +98-711-228-4822; Fax: +98-711-228-0926.
Received: 2 November 2009; in revised form: 3 December 2009 / Accepted: 9 December 2009 /
Published: 22 January 2010
Abstract: Some new mono-and bis-polycyclic aromatic spiro-β-lactams and bis-non spiro-
polycyclic aromatic β-lactams have been synthesized from imines derived from
anthracene-9-carbaldehyde, 2-naphtaldehyde and a ketene derived from 9H-xanthene-9-
carboxylic acid and phenoxyacetic acid by a [2+2] cycloaddition reaction. The
1
13
cycloadducts were characterized by spectral data, including H-NMR, C-NMR, IR and
elemental analyses. The configurations of some of these mono-spiro-β-lactams were
established by X-ray crystal analysis.
Keywords: mono- and bis-spiro-β-lactam; polycyclic aromatic imine; 9H-xanthene-9-
carboxylic acid; phenoxyacetic acid; [2+2] cycloaddition; tosyl chloride
1. Introduction
β-Lactams, being a structural unit found in the most widely used antibiotics [1], have occupied a
basic position in medicinal chemistry for almost a century now. With the microbes responding to the
traditional antibiotics through β-lactamases, the need for novel antibiotics prevails, making synthesis
of newer β-lactams ever more important. In addition to their use as antibiotics, β-lactams are
increasingly being used as synthons for other biologically important molecules [2–11]. β-Lactams have
been found to act as cholesterol acyl transferase inhibitors [12], thrombin inhibitors [13], human
cytomegalovirus protease inhibitors [14], matrix metalloprotease inhibitors [15], cysteine protease [16],
and apoptosis inductors [17]. Spirocyclic β-lactams have attracted attention as they have been shown

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516
to be β-turn mimetics [18–19] and precursors for α,α-disubstituted β-amino acids [20]. The chartelline
has a spiro-β-lactam moiety in its structure marine natural products [21]. It has been found that
spiro-β-lactams act as poliovirus and human rhinovirus 3C-proteinases inhibitors [22]. These
compounds are mostly synthesized by cycloaddition to an exocyclic bond. Several syntheses of
spiro-β-lactams have been reported [23–42]. Polycyclic aromatic β-lactams have shown anticancer and
other biological activities [43–45]. Some polyaromatic β-lactams have been reported to have
polyaromatic ring in part of imines that prepared by Staudinger reaction [46]. Therefore in
continuation of our work on the synthesis of novel β-lactams [47–49], we present here for the first time
the results obtained in the synthesis of mono- and bis-polyaromatic spiro and nonspiro-β-lactams using
a modified Staudinger reaction.
2. Results and Discussion
Treatment of anthracene-9-carbaldehyde or 2-naphtaldehyde with different primary amines in
refluxing ethanol afforded the polycyclic aromatic imines 1a–n [50–53]. These Schiff bases were then
treated with 9H-xanthene-9-carboxylic acid in the presence of triethylamine and tosyl chloride to
afford polycyclic aromatic spiro-β-lactams 2a–n as single diastereomers (Scheme 1). The reaction
progress was monitored by TLC and the presence of a new compound was confirmed. In addition, the
cycloadducts were characterized by spectral analysis. For 2a the IR spectrum showed the characteristic
1
absorption of a β-lactam carbonyl at 1,747 cm−1. The H-NMR spectrum exhibited the methoxy
protons as a singlet at 3.64 ppm, the β-lactam H-4 proton as a singlet at 6.29 and aromatic protons as a
13
multiplet at 6.39–8.82. The C-NMR spectrum exhibited the C-3 (spiro carbon) at 64.3. The results
for other polycyclic aromatic spiro-β-lactams 2a–n are shown in Table 1.
Scheme 1. Synthesis of polycyclic aromatic spiro-β-lactams 2a–n.

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Table 1. Structures of spiro-β-lactams.
Yield (%)
Entry
Product
Yield (%) a
Entry
Product
a
1
25
6
40
2a
2f
2
54
7
35
2b
2g
3
4
5
51
63
70
8
53
70
91
2c
2h
9
2d
2i
10
2e
2j

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Table 1. Cont.
Yield
(%)a
Entry
Product
Yield (%)a
Entry
Product
11
69
68
13
50
2m
2k
12
14
40
2l
2n
a Isolated yield of pure products.
Then we decided to synthesize bis-spiro- and bis-nonspiro- polycyclic aromatic β-lactams 4a–d, 6b
and 4e–h, 6a from bis-imines 3a–d and 5 [53] (Scheme 2). The structures of 4a–h and 5a–b are shown
in Table 2. The cis-trans stereochemistry of 2-azetidinones 4e–h and 6a were deduced from the
coupling constant of H-3 and H-4, which was calculated to be J3,4 = 4–9 Hz for the cis and
J3,4 = 1–3 Hz for the trans stereoisomers.
Scheme 2. Synthesis of bis-spiro- and bis-nonspiro- polycyclic aromatic β-lactams 4a–h and 6a–b.
X
X
9H-xanthene-9-carboxylic acid
or phenoxyacetic acid
N
N
Et3N, TsCl, CH2Cl2
N
N
O
O
R2
R2
4a-h
3a: X= CH2 (4,4')
3b: X= CH2 (3,3')
3c: X= O (4,4')
3d: X= O (3,4')
O
9H-xanthene-9-carboxylic acid
or phenoxyacetic acid
R2
N
N
R2
N
N
Et3N, TsCl, CH2Cl2
O
6a-b
5

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Yield(%)a
87
Table 2. Structures of bis-spiro and bis-nonspiro-β-lactams.
Entry
Product
Yield(%)a Entry
Product
1
92
6
4a
4f
2
3
4
87
96
85
7
8
9
90
95
96
4b
4c
4g
4h
6a
4d
4e
5
80
10
85
6b
a Isolated yields of pure products.
The X-ray crystallography of 2a (Figure 1) confirmed the proposed spiro configuration at C3 [54–59].
The X-ray analysis also showed that the β-lactam ring is planar and it is perpendicular to xanthene
ring. The anthracene ring has dihedral angles of 51.8° with the β-lactam ring.

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Figure 1. X-ray crystal structure of 2a.
3. Experimental Section
3.1. General
All needed chemicals were purchased from the Merck, Fluka or Acros chemical companies. All
reagents and solvents were dried prior to use according to standard methods [60]. IR spectra were run
1
on a Shimadzu FT-IR 8300 spectrophotometer. H-NMR and 13C-NMR spectra were recorded in
DMSO-d6 or CDCl3 using a Bruker Avance DPX instrument (1H-NMR 250 MHz, 13C-NMR 62.9 MHz).
Chemical shifts were reported in parts per million (δ) downfield from TMS. All of the coupling
constants (J) are in hertz. The mass spectra were recorded on a Shimadzu GC-MS QP 1000 EX
instrument. Elemental analyses were run on a Thermo Finnigan Flash EA-1112 series. Melting points
were determined in open capillaries with Buchi 510 melting point apparatus. Thin-layer
chromatography was carried out on silica gel F254 analytical sheets obtained from Fluka. Column
chromatography was performed on Merck Kiesel gel (230–270 mesh).
3.2. General Procedure for Preparation of Schiff Bases 1a–n
A mixture of an aromatic amine (1.00 mmol) and anthracene-9-carbaldehyde or 2-naphtaldehyde
(1.00 mmol) was refluxed in ethanol (20 mL) for 1–5 hours. After cooling, the pure Schiff bases were
separated as crystals. Some of these were recrystallized from ethanol.
(E)-N-(Anthracen-10-ylmethlene)-4-methxybenzenamine (1a): Yellow powder crystal (yield 91%);
Mp: 140–148 °C; IR (CHCl3, cm−1): 1,608 (C=N); 1H-NMR δ (ppm): 3.88 (OMe, s, 3H), 6.52–7.64

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(ArH, m, 13H), 9.80 (CHN, s, 1H). Analysis calculated for C22H17NO: C, 84.86; H, 5.50; N, 4.50%.
Found: C, 84.83; H, 5.55; N, 4.48%.
(E)-N-(Anthracen-10-ylmethylene)-3-methoxybenzenamine (1b): Yellow powder crystal (yield 84%);
Mp: 100–102 °C; IR (CHCl3, cm−1): 1,608 (C=N); 1H-NMR δ (ppm): 3.87 (OMe, s, 3H), 6.89–8.74
(ArH, m, 13H), 9.66 (CHN, s, 1H). Analysis calculated for C22H17NO: C, 84.86; H, 5.50; N, 4.50%.
Found: C, 84.83; H, 5.55; N, 4.48%.
(E)-N-(Anthracen-10-ylmethylene)-2-methoxybenzenamine (1c): Orange powder crystal (yield 76%);
Mp: 94–96 °C; IR (CHCl3, cm−1): 1,620 (C=N); 1H-NMR δ (ppm): 6.73–8.75 (ArH, m, 13H), 9.66
(CHN, s, 1H). Analysis calculated for C22H17NO: C, 84.86; H, 5.50; N, 4.50%. Found: C, 84.83; H,
5.55; N, 4.48%.
(E)-N-(Anthracen-10-ylmethylene)benzenamine (1d): Yellow powder crystal (yield 76%);
Mp: 102–104 °C; IR (KBr, cm−1): 1,608 (C=N); 1H-NMR δ (ppm): 6.61–8.96 (ArH, m, 14H), 9.63
(CHN, s, 1H). Analysis calculated for C21H15N: C, 89.65; H, 5.37; N, 4.98%. Found: C, 89.61;
H, 5.41; N, 4.95%.
(E)-N-(Anthracen-10-ylmethylene)-4-chlorobenzenamine (1e): Yllow crystal (yield 51%);
Mp: 182–184 °C; IR (KBr, cm−1): 1,623 (C=N); 1H-NMR δ (ppm): 6.64–8.72 (ArH, m, 13H), 9.61
(CHN, s, 1H). Analysis calculated for C21H14ClN: C, 79.87; H, 4.47; N, 4.44%. Found: C, 79.85;
H, 4.50; N, 4.49%.
(E)-N-(Anthracen-10-ylmethylene)-3-nitrobenzenamine (1f): Orange crystal (yield 67%);
Mp: 166–168 °C; IR (KBr, cm−1): 1,666 (C=N); 1H-NMR δ (ppm): 6.62–8.96 (ArH, m, 13H), 9.66
(CHN, s, 1H). Analysis calculated for C21H14N2O2: C, 77.29; H, 4.32; N, 8.58%. Found: C, 77.35;
H, 4.38; N, 8.60%.
(E)-N-(Anthracen-10-ylmethylene)-2-ethylbenzenamine (1g): Yellow crystal (yield 60%);
Mp: 182–184 °C; IR (CHCl3, cm−1): 1,620 (C=N); 1H-NMR δ (ppm): 1.27 (CH2, t, 2H, J = 7.5), 2.89
(CH3, q, 4H, J = 7.5), 6.82–8.80 (ArH, m, 13H), 9.55 (CHN, s, 1H). Analysis calculated for C23H19N:
C, 89.28; H, 6.19; N, 4.53%. Found: C, 89.32; H, 6.25; N, 4.55%.
(E)-N-(Anthracen-10-ylmethylene)-3-bromobenzenamine (1h): Yellow crystal (yield 77%);
Mp: 122–124 °C; IR (KBr, cm−1): 1,620 (C=N); 1H-NMR δ (ppm): 6.84–8.71 (ArH, m, 13H), 9.60
(CHN, s, 1H). Analysis calculated for C21H14BrN: C, 70.01; H, 3.92; N, 3.89%. Found: C, 70.11;
H, 3.98; N, 3.84%.
(E)-N-(Anthracen-10-ylmethylene)-2,4-dimethoxybenzenamine (1i): Orange crystal (yield 88%);
1
Mp: 160–162 °C; IR (CHCl3, cm−1): 1,616 (C=N); H-NMR δ (ppm): 3.75, 3.98 (2OMe, s, 6H),
6.51–8.73 (ArH, m, 12H), 9.92 (CHN, s, 1H). Analysis calculated for C23H19NO2: C, 80.92; H, 5.61;
N, 4.10%. Found: C, 80.96; H, 5.66; N, 4.17%.

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(E)-N-(Anthracen-10-ylmethylene)-3,4-dimethoxybenzenamine (1j): Orange crystal (yield 90%);
1
Mp: 160–162 °C; IR (CHCl3, cm−1): 1,605 (C=N); H-NMR δ (ppm): 3.88, 3.91 (2OMe, s, 6H),
6.88–8.68 (ArH, m, 12H), 9.92 (CHN, s, 1H). Analysis calculated for C23H19NO2: C, 80.92; H, 5.61;
N, 4.10%. Found: C, 80.96; H, 5.66; N, 4.17%.
(E)-N-(Anthracen-10-ylmethylene)cyclohexanamine
(1k):
Orange
crystal
(yield
92%);
Mp: 132–134 °C; IR (CHCl3, cm−1): 1,639 (C=N); 1H-NMR δ (ppm): 1.34–3.56 (cyclohexyl, m, 11H),
7.41–8.43 (ArH, m, 9H), 9.34 (CHN, s, 1H). Analysis calculated for C21H21N: C, 87.76; H, 7.36; N,
4.87%. Found: C, 87.71; H, 7.33; N, 4.91%.
(E)-N-(Anthracen-10-ylmethlene)naphthalene-1-amine (1l): Yellow crystal (yield 60%);
Mp: 142–144° C; IR (CHCl3, cm−1): 1,624 (C=N); 1H–NMR δ (ppm): 6.67–8.94 (Ar-H, m, 16H), 8.80
(CHN, s, 1H). Analysis calculated for C25H17N: C, 90.60; H, 5.17; N, 4.23%. Found: C, 90.66;
H, 5.20; N, 4.28%.
(E)-N-(Naphthalen-2-ylmethylene)naphthalen-1-amine (1m): Green crystal (yield 78%);
Mp: 129–130° C. IR (CHCl3, cm−1): 1,624 (C=N); 1H–NMR δ (ppm): 6.73–8.63 (Ar-H, m, 14H), 8.94
(CHN, s, 1H). Analysis calculated for C25H17N: C, 90.60; H, 5.17; N, 4.23%. Found: C, 90.66; H, 5.20;
N, 4.28%.
(E)-4-Methoxy-N-(naphthalen-2-ylmethylene)benzenamine (1n): Silver powder crystal (yield 80%);
Mp: 118–120° C; IR (CHCl3, cm−1): 1,620 (C=N); 1H-NMR δ (ppm): 3.78 (OMe, s, 3H), 6.90–8.13
(ArH, m, 11H), 8.60 (CHN, s, 1H). Analysis calculated for C18H15NO: C, 82.73; H, 5.79; N, 5.36%.
Found: C, 82.75; H, 5.83; N, 5.32%.
3.3. General Procedure for Preparation of Bis-Schiff Bases 3a–d and 5
A mixture of anthracene-9-carbaldehyde (1.00 mmol) and bisamine (0.50 mmol) was refluxed in
ethanol (20 mL) for (1–5) h. After cooling, the pure Schiff bases were separated as crystals. Some of
these were recrystallized from ethanol.
(E)-4-(E)-4-[(E)-Anthracen-10-ylmethyleneamino)benzyl]-N-(anthracen-10-ylmethylene)benzene-
amine (3a): Yellow powder (yield 96%); Mp: 216–218 °C; IR (KBr, cm−1): 1,623 (C=N); 1H-NMR
δ (ppm): 4.15 (CH2, s, 2H), 6.68–9.70 (ArH, m, 26H), 10.02 (CH=N, s, 2H); Analysis calculated for
C43H30N2: C, 89.86; H, 5.26; N, 4.87%. Found: C, 89.81; H, 5.22; N, 4.83%.
(E)-3-(E)-3-[(E)-Anthracen-10-ylmethyleneamino)benzyl]-N-(anthracen-10-yl-methylene)benzenenamine
(3b): Yellow powder (yield 95%); Mp: 184–186 °C; IR (KBr, cm−1): 1,623 (C=N); 1H-NMR δ (ppm):
4.19 (CH2, s, 2H), 7.24–8.92 (ArH, m, 26H), 9.73 (CH=N, s, 2H); Analysis calculated for C43H30N2:
C, 89.86; H, 5.26; N, 4.87%. Found: C, 89.81; H, 5.22; N, 4.83%.

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(E)-N-(Anthracen-10-yl-methylene)-4-(4-[(E)-anthracen-10-ylmethyleneamino]phenoxy)benzene-
amine (3c): Orange powder (yield 96%); Mp: 202–204 °C; IR (KBr, cm−1): 1,608 (C=N); 1H-NMR δ
(ppm): 6.73–8.78 (ArH, m, 26H), 9.60 (CH=N, s, 2H); Analysis calculated for C42H28N2O: C, 87.47;
H, 4.89; N, 4.86%. Found: C, 87.51; H, 4.95; N, 4.81%.
(E)-N-(Anthracen-10-ylmethylene)-3-(4-[(E)-anthracen-10-ylmethyleneamino]phenoxy)benzeneamine
(3d): Yellow powder (yield 88%); Mp: 216–218 °C; IR (KBr, cm−1): 1,620 (C=N); 1H-NMR δ (ppm):
6.20–9.01 (ArH, m, 26H), 9.71 (CH=N, s, 2H); Analysis calculated for C42H28N2O: C, 87.47; H, 4.89;
N, 4.86%. Found: C, 87.51; H, 4.95; N, 4.81%.
(N1E,N4E)-N1,N4-bis(Anthracen-10-ylmethylene)benzene-1,4-diamine (5): Yellow powder (yield 95%);
Mp: > 240 °C; IR (KBr, cm−1): 1,604 (C=N); 1H-NMR δ (ppm): 7.25–8.84 (ArH, m, 22H), 9.81 (CHN,
s, 2H). Analysis calculated for C36H24N2: C, 89.23; H, 4.99; N, 5.78%. Found: C, 89.28; H, 5.05;
N, 5.73%.
3.4. General Procedure for the Synthesis of Polycyclic Aromatic Spiro-β-Lactams 2a–n
A mixture of Schiff base (1.00 mmol), triethylamine (5.00 mmol), 9H-xanthene-9-carboxylic acid
(1.50 mmol) and tosyl chloride (1.50 mmol) in dry CH2Cl2 (15 mL) was stirred at room temperature
for 24 h. Then it was washed with HCl 1N (20 mL), saturated NaHCO3 (20 mL) and brine (20 mL).
The organic layer was dried (Na2SO4), filtered and the solvent was evaporated to give the product as a
crystal which was then purified by recrystallization from appropriate organic solvents.
2-(Anthracen-9-yl)-1-(4-methoxyphenyl)spiro[azetidine-3,9'-xanthen]-4-one (2a): Light yellow
crystals from EtOAc (yield 25%); Mp: 223–225 °C; IR (CHCl3, cm−1): 1,740 (CO β-lactam); 1H-NMR
δ (ppm): 3.64 (OMe, s, 3H) 6.29 (H-4, s, 1H), 6.51–8.82 (ArH, m, 21H); 13C-NMR δ (ppm) 64.3
(OMe) 82.8 (C-3), 75.6 (C-4), 116.4–152.2 (aromatic carbon), 167.3 (CO β-lactam);
GC-MS m/z = 519 [M+]; Analysis calculated for C36H25NO3: C, 83.22; H, 4.85; N, 2.70%.
Found: C, 83.95; H, 4.90; N, 2.82.
2-(Anthracen-9-yl)-1-(3-methoxyphenyl)spiro[azetidine-3,9'-xanthen]-4-one (2b): Yellow crystals
1
from EtOAc (yield 54%); Mp: 212–214 °C; IR (CHCl3, cm−1): 1,755 (CO β-lactam); H-NMR δ
(ppm): 3.75 (OMe, s, 3H) 6.33 (H-4, s, 1H), 6.53–8.80 (ArH, m, 21H);
13C-NMR δ (ppm): 55.3 (OMe) 65.6 (C-3), 75.6 (C-4), 103.5–160.4 (aromatic carbon), 167.6 (CO
β-lactam); GC-MS m/z = 519 [M+]; Analysis calculated for C36H25NO3: C, 83.22; H, 4.85; N, 2.70%.
Found: C, 83.95; H, 4.90; N, 2.82%.
2-(Anthracen-9-yl)-1-(2-methoxyphenyl)spiro[azetidine-3,9'-xanthen]-4-one (2c): Light yellow
crystals from EtOAc (yield 57%); Mp: 214–216 °C (dec.); IR (KBr, cm−1): 1,739 (CO β-lactam);
1H-NMR δ (ppm): 2.94 (OMe, s, 3H), 6.34 (H-4, s, 1H), 6.55–9.20 (ArH, m, 21H);
13C-NMR δ (ppm): 55.4 (OMe), 66.0 (C-3), 78.5 (C-4), 112.8–152.0 (aromatic carbon), 168.0 (CO
β-lactam); GC-MS m/z = 519 [M+]; Analysis calculated for C36H25NO3: C, 83.22: H, 4.85; N, 2.70%.
Found: C, 83.90; H, 4.80; N, 2.81%.

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2-(Anthracen-9-yl)-1-phenylspiro[azetidine-3,9'-xanthen]-4-one (2d): Light yellow crystals from
EtOAc (yield 63%); Mp: 238–240 °C (dec.); IR (KBr, cm−1): 1,758 (CO β-lactam);
1H-NMR δ (ppm): 6.34 (H-4, s, 1H), 6.51–8.83 (ArH, m, 22H); 13C-NMR δ (ppm): 65.6 (C-3),
75.4 (C-4), 115.9–152.0 (aromatic carbon), 167.5 (CO β-lactam); GC-MS m/z = 489 [M+]; Analysis
calculated for C35H23NO2: C, 85.87; H, 4.74; N, 2.86%. Found: C, 85.87; H, 4.74; N 2.86%.
2-(Anthracen-9-yl)-1-(4-chlorophenyl)spiro[azetidine-3,9'-xanthen]-4-one (2e): Yellow crystals from
EtOAc (yield 70%); Mp: 254–256 °C (dec.); IR (KBr, cm−1): 1,743 (CO β-lactam); 1H-NMR δ (ppm):
13
6.30 (H-4, s, 1H), 6.52–9.06 (ArH, m, 21H); C-NMR δ (ppm): 66.0 (C-3), 75.5 (C-4), 116.0–151.9
(aromatic carbon), 167.4 (CO β-lactam); GC-MS m/z = 524 [M+, 35Cl], 526 [M+, 37Cl]; Analysis
calculated for C35H22ClNO2: C, 80.22; H, 4.23; N 2.67%. Found: C, 80.28; H, 4.18; N, 2.53%.
2-(Anthracen-9-yl)-1-(3-nitrophenyl)spiro[azetidine-3,9'-xanthen]-4-one (2f): Yellow crystals from
1
EtOAc (yield 40%); Mp: 212–214 °C; IR (KBr, cm−1): 1,762 (CO β-lactam); H-NMR δ (ppm):
13
5.98 (H-4, s, 1H), 6.40–9.16 (ArH, m, 21H); C-NMR δ (ppm): 66.4 (C-3), 75.8 (C-4), 112.4–152.1
(aromatic carbon), 169.2 (CO β-lactam); GC-MS m/z = 534 [M+]; Analysis calculated for C35H22N2O4:
C, 78.64; H, 4.15; N, 5.24%. Found: C, 78.63; H, 4.20; N, 5.32%.
2-(Anthracen-9-yl)-1-(2-ethylphenyl)spiro[azetidine-3,9'-xanthen]-4-one (2g): White solid (yield
1
35%); Mp: 208–210 °C; IR (KBr, cm−1): 1,755 (CO β-lactam); H-NMR δ (ppm): 1.14 (t, 3H, Me,
13
J = 7.1), 4.00 (CH2, q, 2H, J = 7.1), 4.92 (s, 1H, H-4), 6.30–8.74 (ArH, m, 21H); C-NMR δ (ppm):
15.1 (CH3), 25.8 (CH2), 64.5 (C-3), 75.1 (C-4), 115.9–152.2 (aromatic carbon), 168.1 (CO β-lactam);
GC-MS m/z = 517 [M+]; Analysis calculated for C37H27NO2: C, 85.85; H, 5.26; N, 2.71%. Found:
C, 85.83; H, 5.30; N, 2.76%.
2-(Anthracen-9-yl)-1-(3-bromophenyl)spiro[azetidine-3,9'-xanthen]-4-one (2h): Yellow crystals from
1
EtOAc (yield 55%); Mp: 222–224 °C; IR (KBr, cm−1): 1,755 (CO β-lactam); H-NMR δ (ppm): 6.18
(H-4, s, 1H), 6.23–8.65 (ArH, m, 21H); 13C-NMR δ (ppm): 66.0 (C-3), 75.6 (C-4), 115.7–151.9
(aromatic carbon), 167.7 (CO β-lactam); GC-MS m/z = 567 [M+, 80Br], 569 [M+, 82Br]; Analysis
calculated for C35H22BrNO2: C, 73.95; H, 3.90; N, 2.46%. Found: C, 73.90; H, 3.93; N, 2.51%.
2-(Anthracen-9-yl)-1-(2,4-dimethoxyphenyl)spiro[azetidine-3,9'-xanthen]-4-one (2i): Light green
crystals from EtOAc (yield 69%); Mp: 180–182 °C (dec.); IR (KBr, cm−1): 1,739 (CO β-lactam);
1H-NMR δ (ppm): 2.91, 3.58 (2OMe, s, 6H) 6.16 (H-4, s, 1H), 6.17–8.18 (ArH, m, 20H);
13C-NMR δ (ppm): 55.4, 55.5 (s, 6H, 2 OMe) 65.9 (C-3), 78.1 (C-4), 100.2–158.2 (aromatic carbon),
167.7 (CO β-lactam); GC-MS m/z = 549 [M+]; Analysis calculated for C37H27NO4: C, 80.86; H, 4.95;
N, 2.55%. Found: C, 80.03; H, 4.98; N, 2.83%.
2-(Anthracen-9-yl)-1-(3,4-dimethoxyphenyl)spiro[azetidine-3,9'-xanthen]-4-one (2j): Yellow solid
1
(yield 91%); Mp: 172–174 °C; IR (KBr, cm−1): 1,743 (CO β-lactam); H-NMR δ (ppm): 3.69, 3.97
13
(2OMe, s, 6H) 6.30 (H-4, s, 1H), 6.50–8.77 (ArH, m, 20H); C-NMR δ (ppm): 55.9, 56.1 (2 OMe)
65.6 (C-3), 75.6 (C-4), 102.3–153.0 (aromatic carbon), 166.9 (CO β-lactam); GC-MS m/z = 549 [M+];

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Analysis calculated for C37H27NO4: C, 80.86; H, 4.95; N, 2.55%. Found: C, 80.81; H, 4.97;
N, 2.53%.
2-(Anthracen-9-yl)-1-cyclohexylspiro[azetidine-3,9'-xanthen]-4-one (2k): Orange crystals from
1
EtOAc (yield 69%); Mp: 216–218 °C; IR (KBr, cm−1): 1,743 (CO β-lactam); H-NMR δ (ppm): 1.53,
1.75, 1.95, 2.22, 2.65, 3.81 (cyclohexyl, m, 11H) 5.96 (H-4, s, 1H), 6.36–9.19 (ArH, m, 17H);
13C-NMR δ (ppm): 24.5, 25.5, 30.0, 31.0, 56.7 (cyclohexyl) 64.5 (C-3), 72.8 (C-4), 115.9–152.4
(aromatic carbon), 169.6 (CO β-lactam); GC-MS m/z = 495 [M+]; Analysis calculated for C35H29NO2:
C, 84.82; H, 5.90; N, 2.83%. Found: C, 84.81; H, 5.92; N, 2.81%.
2-(Anthracen-9-yl)-1-(naphthalen-1-yl)spiro[azetidine-3,9'-xanthen]-4-one (2l): Orange crystals from
EtOAc (yield 68%); Mp: 184–186 °C (dec.); IR (CHCl3, cm−1): 1,759 (CO β-lactam);
1H-NMR δ (ppm): 6.45 (H-4, s, 1H), 6.61–9.8 (ArH, m, 24H); 13C-NMR δ (ppme) 90.3 (C-3), 74.8 (C-4),
116.7–152.1 (aromatic carbon), 168.3 (CO β-lactam); GC-MS m/z = 539 [M+]; Analysis calculated for
C39H25NO2: C, 86.80; H, 4.67; N, 2.60%. Found: C, 86.52; H, 4.63; N, 2.61%.
1-(Naphthalen-1-yl)-2-(naphthalen-2-yl)spiro[azetidine-3,9'-xanthen]-4-one (2m): White solid (yield
1
50%); Mp: 187–189 °C; IR (KBr, cm−1): 1,758 (CO β-lactam); H-NMR δ (ppm) 5.73 (H-4, s, 1H),
6.50–9.00 (ArH, m, 22H); 13C-NMR δ (ppm): 62.8 (C-3), 75.8 (C-4), 116.4–152.29 (aromatic carbon),
196.3 (CO β-lactam); GC-MS m/z = 489 [M+]; Analysis calculated for C35H23NO2: C, 85.87; H, 4.74;
N, 2.86%. Found: C, 85.67; H, 4.65; N, 2.79%.
1-(4-Methoxyphenyl)-2-(naphthalen-2-yl)spiro[azetidine-3,9'-xanthen]-4-one (2n): Gray solid (yield
40%); Mp: 184–186 °C; IR (CHCl3, cm−1): 1,751 (CO β-lactam); 1H-NMR δ (ppm): 3.81 (OMe, s, 3H)
13
5.21 (H-4, s, 1H), 6.64–8.33 (ArH, m, 19H); C-NMR δ (ppm): 55.5 (OMe) 64.0 (C-3), 74.6 (C-4),
113.9–151.8 (aromatic carbon), 167.0 (CO β-lactam); GC-MS m/z = 469 [M+]; Analysis calculated for
C32H23NO3: C, 81.86; H, 4.94; N, 2.98%. Found: C, 81.53; H, 4.98; N, 2.83%.
3.5. General Procedure for the Synthesis of Bis-Polycyclic Aromatic Spiro and Nonspiro-β-Lactams
4a–h and 6a–b
A mixture of Schiff base (1.00 mmol), triethylamine (10.00 mmol), 9H-xanthen-9-carboxylic acid
or phenoxyacetic acid (3.00 mmol) and tosyl chloride (3.00 mmol) in dry CH2Cl2 (15 mL) was stirred
at room temperature for 24 h. Then it was washed with HCl 1N (20 mL), saturated NaHCO3 (20 mL)
and brine (20 mL). The organic layer was dried (Na2SO4), filtered and the solvent was evaporated to
give the product as a crystal which was then purified by recrystallization from suitable organic
solvents.
2-(Anthracen-9-yl)-1-(4-(4-(2-(anthracen-9-yl)-4-oxospiro[azetidine-3,9'-xanthene]-1-yl)benzyl)-
phenyl)spiro[azetidine-3,9'-xanthen]-4-one (4a): Orange solid (yield 92%); Mp: 162–164 °C (dec.); IR
1
(KBr, cm−1): 1,755 (CO β-lactam); H-NMR δ (ppm): 3.76 (CH2, s, 2H) 6.15 (H-4, s, 2H), 6.19–8.99
(ArH, m, 42H); 13C-NMR δ (ppm): 40.8 (CH2) 65.7 (C-3), 75.4 (C-4), 115.9–152.0 (aromatic carbon),
167.3 (CO β-lactam). Analysis calculated for C71H46N2O4: C, 86.04; H, 4.68; N, 2.83%. Found: C,
86.10; H, 4.71; N, 2.80%.

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2-(Anthracen-9-yl)-1-(3-(3-(2-(anthracen-9-yl)-4-oxospiro[azetidine-3,9'-xanthene]-1-yl)benzyl)
phenyl)spiro[azetidine-3,9'-xanthen]-4-one (4b): Orange solid (Yield 87%); Mp: 220–222 °C (dec.);
IR (KBr, cm−1): 1,758 (CO β-lactam); 1H-NMR δ (ppm): 3.78 (CH2, s, 2H,) 6.22 (H-4, s, 2H), 6.26–9.52
(ArH, m, 42H); 13C-NMR δ (ppm): 41.5 (CH2) 59.6 (C-3), 75.4 (C-4), 115.9–152.0 (aromatic carbon),
167.4 (CO β-lactam). Analysis calculated for C71H46N2O4: C, 86.04; H, 4.68; N, 2.83%. Found:
C, 86.06; H, 4.70; N, 2.80%.
2-(Anthracen-9-yl)-1-(4-(4-(2-(anthracen-9-yl)-4-oxospiro[azetidine-3,9'-xanthene]-1-yl)phenoxy)
phenyl)spiro[azetidine-3,9'-xanthen]-4-one (4c): Yellow solid (Yield 75%); Mp: 242–244 °C (dec.);
IR (KBr, cm−1): 1,755 (CO β-lactam); 1H-NMR δ (ppm): 6.20 (H-4, s, 2H), 6.22–8.68 (ArH, m, 42H);
13C-NMR δ (ppm): 65.8 (C-3), 75.5 (C-4), 115.9–153.9 (aromatic carbon), 167.0 (CO β-lactam).
Analysis calculated for C70H44N2O5: C, 84.66; H, 4.47; N, 2.82%. Found: C, 84.64; H, 4.48; N, 2.80%.
2-(Anthracen-9-yl)-1-(3-(4-(2-(anthracen-9-yl)-4-oxospiro[azetidine-3,9'-xanthene]-1-yl)phenoxy)
phenyl)spiro[azetidine-3,9'-xanthen]-4-one (4d): Orange solid (Yield 85%); Mp: 140–142 °C;
IR (KBr, cm−1): 1,759 (CO β-lactam); 1H-NMR δ (ppm): 6.15 (H-4, s, 2H), 6.40–8.79 (ArH, m, 42H).
13C-NMR δ (ppm): 65.8 (C-3), 75.7 (C-4), 117.5–157.4 (aromatic carbon), 167.4 (CO β-lactam).
Analysis calculated for C70H44N2O5: C, 84.66; H, 4.47; N, 2.82%. Found: C, 84.63; H, 4.45; N, 2.81%.
1,1'-(4,4'-Methylenebis(4,1-phenylene))bis(4-(anthracen-9-yl)-3-phenoxyazetidin-2-one) (4e): Yellow
1
solid (Yield 80%); Mp: 146–148 °C; IR (KBr, cm−1): 1,755 (CO β-lactam); H-NMR δ (ppm): 3.42
(CH2, s, 2H) 5.85 (H-4, d, 2H, J = 2.8), 6.40 (H-3, d, 2H, J = 2.8), 6.47–9.54 (ArH, m, 36H); 13C-NMR
δ (ppm): 40.5 (CH2) 62.9 (C-3), 59.1 (C-4), 115.6–157.1 (aromatic carbon), 163.3 (CO β-lactam).
Analysis calculated for C59H42N2O4: C, 84.06; H, 5.02; N, 3.32%. Found: C, 84.10; H, 5.08; N, 3.35%.
1,1'-(3,3'-Methylenebis(3,1-phenylene))bis(4-(anthracen-9-yl)-3-phenoxyazetidin-2-one) (4f): Orange
1
solid (Yield 87%); Mp: 118–120 °C; IR (KBr, cm−1): 1,758 (CO β-lactam); H-NMR δ (ppm): 3.47
(CH2, s, 2H) 5.71 (H-4, d, 2H, J = 3.6), 6.38 (H-3, d, 2H, J = 3.6), 6.41–9.41 (ArH, m, 36H); 13C-NMR
δ (ppm): 41.1 (CH2) 82.6 (C-3), 60.6 (C-4), 115.5–157.1 (aromatic carbon), 163.4 (CO β-lactam);
Analysis calculated for C59H42N2O4: C, 84.06; H, 5.02; N, 3.32%. Found: C, 84.08; H, 5.05; N, 3.30%.
1,1'-(4,4'-Oxybis(4,1-phenylene))bis(4-(anthracen-9-yl)-3-phenoxyazetidin-2-one) (4g): Orange solid
(Yield 90%); Mp: 126–128 °C; IR (KBr, cm−1): 1,755 (CO β-lactam); 1H-NMR δ (ppm): 5.71 (H-4, d,
2H, J = 5.1), 6.20 (H-3, d, 2H, J = 5.1), 6.36–8.78 (m, ArH, 36H);13C-NMR δ (ppm): 83.1 (C-3), 59.2
(C-4), 115.6–133.0 (aromatic carbon), 167.7 (CO β-lactam). Analysis calculated for C58H40N2O5:
C, 82.45; H, 4.77; N, 3.32%. Found: C, 82.41; H, 4.79; N, 3.35%.
4-(Anthracen-9-yl)-1-(3-(4-(2-(anthracen-9-yl)-4-oxo-3-phenoxyazetidin-yl)phenoxy)phenyl)-3-phen
oxyazetidin-2-one (4h): Yellow solid (Yield 95%); Mp: 118–120 °C; IR (KBr, cm−1): 1,758 (CO
β-lactam); 1H-NMR δ (ppm): 5.75 (H-4, d, 2H, J = 3.8), 6.25 (H-3, d, 2H, J = 3.8), 6.42–8.79 (ArH, m,
36H); 13C-NMR δ (ppm): 83.1 (C-3), 65.4 (C-4), 107.7–157.4 (aromatic carbon), 163.5 (CO β-lactam).
Analysis calculated for C58H40N2O5: C, 82.45; H, 4.77; N, 3.32%. Found: C, 82.43; H, 4.75; N, 3.30%.

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1,1'-(1,4-Phenylene)bis(4-(anthracen-9-yl)-3-phenoxyazetidin-2-one) (6a): Gray solid (Yield 96%);
1
Mp: 178–180 °C (dec.); IR (KBr, cm−1): 1,751 (CO β-lactam); H-NMR δ (ppm): 5.58 (H-4, d, 2H,
J = 3.9), 6.30 (H-3, d, 2H, J = 3.9), 6.33–8.82 (ArH, m, 32H);13C-NMR δ (ppm): 83.0 (C-3), 59.1 (C-
4), 114.6–156.8 (aromatic carbon), 163.0 (CO β-lactam). Analysis calculated for C52H36N2O4: C,
82.96; H, 4.82; N, 3.72% Found: C, 82.95; H, 4.81; N, 3.70%.
1,1'-(1,4-Phenylene)bis(2-(anthracen-9-yl)spiro[azetidine-3,9'-xanthen]-4-one) (6b): Orange solid
1
(Yield 85%); Mp: 186–188 °C (dec.); IR (KBr, cm−1): 1,751 (CO β-lactam); H-NMR δ (ppm): 6.27
(H-4, s, 2H), 6.30–8.99 (ArH, m, 38H); 13C-NMR δ (ppm): 59.7 (C-3), 75.2 (C-4), 115.9–152.0
(aromatic carbon), 167.0 (CO β-lactam). Analysis calculated for C64H40N2O4: C, 85.31; H, 4.47; N,
3.11%. Found: C, 85.30; H, 4.45; N, 3.15%.
4. Conclusions
This article describes for the first time the synthesis and characterization of some examples of
mono-and bis-spiro- and nonspiro-β-lactams bearing a polycyclic aromatic moiety by reaction of
polycyclic aromatic imines and two ketenes derived from 9H-xanthene-9-carboxylic acid and
phenoxyacetic acid. These ketenes were prepared in situ with triethylamine and p-toluenesulfonyl
chloride.
Acknowledgements
The authors thank the Shiraz University Research Council for financial support (Grant No. 88-GR-
SC-23).
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© 2010 by the authors; licensee Molecular Diversity Preservation International, Basel, Switzerland.
This article is an open-access article distributed under the terms and conditions of the Creative
Commons Attribution license (http://creativecommons.org/licenses/by/3.0/).